A clinical trial to evaluate AZD7648 alone and in combination with other anti-cancer agents in patients with advanced cancers.

Study identifier:D9170C00001

ClinicalTrials.gov identifier:NCT03907969

EudraCT identifier:2018-003688-73

CTIS identifier:N/A

Study Complete

Official Title

A Phase I/IIa, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD7648 Monotherapy or in Combination with either Cytotoxic Chemotherapies or Novel Anti-Cancer Agents in Patients with Advanced Malignancies

Medical condition

Advanced Malignancies

Phase

Phase 1/2

Healthy volunteers

Study drug

AZD7648, PLD

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 09 Oct 2019

Primary Completion Date: 07 Dec 2022

Study Completion Date: 07 Dec 2022

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2024 by AstraZeneca

Collaborators

Parexel International

Inclusion and exclusion criteria

Inclusion Criteria

1. Capable and willing to give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
2. Participant must be at least 18 years of age, at the time of signing the ICF.
3. Participants must have histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment.
4. Eastern cooperative oncology group performance status 0-1.
5. Life expectancy greater than 12 weeks.
6. Progressive cancer at the time of study entry.
7. Pharmacodynamics expansion cohorts: Participants must have at least 1 tumour suitable for biopsy and consent to having biopsies collected.
8. Negative pregnancy test (urine or serum) prior to start of dosing for women of childbearing potential.
9. Female participants must be post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 12 weeks after the last dose of study treatment to prevent pregnancy.
10. For the duration of the study (from the time they sign consent) and for 12 weeks after the last dose of study treatment, sexually active male participants must be willing to use contraception.
Post-menopausal is defined as:
- No menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the post-menopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy). However in the absence of 12 months of amenorrhea, a FSH measurement is insufficient.
- Radiation-induced oophorectomy with last menses greater than 12 months ago.
- Chemotherapy-induced menopause with greater than 12 month interval since last menses.
- Surgical sterilisation.

Exclusion Criteria

1. Any unresolved toxicities from prior therapy common terminology criteria for adverse event (CTCAE) Grade ≥2 (with the exception of alopecia).
2. Spinal cord compression or brain metastases unless definitively treated, asymptomatic, stable and not requiring steroids for at least 4 weeks.
3. As judged by the Investigator, any evidence of severe or uncontrolled medical conditions including but not limited to:
• Uncontrolled diabetes mellitus, uncontrolled seizures, active infection requiring systemic antibiotics, antifungal or antiviral drugs, severe chronic obstructive pulmonary disease, severe Parkinson’s disease, active inflammatory bowel disease, psychiatric condition, active bleeding diatheses, renal transplant, or active infection including any participant with active hepatitis B, hepatitis C or human immunodeficiency virus.
4. Any other malignancy which has been active or treated within the past 3 years, with the exception of in situ cancer of the cervix, non-melanoma skin cancer, ductal carcinoma in situ, Stage 1 Grade 1 endometrial carcinoma, or other solid tumours including lymphomas curatively treated with no evidence of disease for ≥5 years.
5. Refractory nausea and vomiting or unable to swallow and retain oral medication, chronic gastrointestinal diseases or previous bowel resection with clinically significant sequelae that would preclude adequate absorption of AZD7648, gastrointestinal symptoms CTCAE Grade >1, history of gastrointestinal ulceration and gastrointestinal haemorrhage within 6 months of first study drug administration.
6 Receiving or having received anti-cancer treatment within the following periods prior to the first dose of investigational product:
(a) Cytotoxic treatment: 3 weeks, (b) Non-cytotoxic drugs: including small molecule investigational products: 3 weeks or 5 half-lives (whichever is longest), (c) Biological products including investigational immuno-oncology agents: 4 weeks, (d) Radiation with a limited field for palliation: 1 week (3 months for radiation to the abdomen or pelvis), (e) Radiation to >30% of the bone marrow or with a wide field: 4 weeks, (f) Lung radiation: 60 days, (g) Major surgery: 4 weeks; minor surgery or biopsy: 1 week
7. During the 4 weeks prior to the first dose, receiving corticosteroids at a dose of >10 mg prednisone/day or equivalent for any reason. Ongoing low dose steroids for longer than 3 months (excluding inhalational, nasal, creams, lotions, and gels) are not allowed.
8. Receiving or having received concomitant medications, herbal supplements and/or foods known to significantly modulate CYP3A4 activity.
9. Prior exposure to a deoxyribonucleic acid-pharmacokinetics inhibitor or hypersensitivity to any excipient of the product.
10. Cardiac dysfunction as defined by any of the following within 6 months of study entry:
(a) Acute myocardial infarction, (b) New York Heart Association Class II/III/IV heart failure, (c) Unstable angina, (d) Unstable cardiac arrhythmias
11. Any of the following cardiac criteria:
(a) Known reduced left ventricular ejection fraction below the institutional lower limit of normal, (b) Mean resting corrected QT interval (QTc) >470 milliseconds obtained from 3 electrocardiograms in 24 hours using the Fridericia formula, (c) Any factors that increase the risk of QTc prolongation or arrhythmic events such as hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age
12. Inadequate hematological or organ function
13. Involvement in the planning and/or conduct of the study.
14. Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
15. Previous enrolment in the present study.
16. For female participant only: currently pregnant or breast-feeding.
17. For food effect cohort only: insulin dependent diabetes.
18. History and/or presence of coronavirus disease 2019.

Location

Research Site

Houston, TX, United States, 77030

Location

Research Site

New Haven, CT, United States, 06510

Location

Research Site

London, United Kingdom, EC1A 7BE

Location

Research Site

Newcastle upon Tyne, United Kingdom, NE7 7DN

Location

Research Site

London, United Kingdom, SE1 9RT

Arms	Assigned Interventions
Experimental: Core Module: AZD7648 Monotherapy AZD7648 will be administered orally on an empty stomach	Drug: AZD7648 Core: AZD7648 will be administered orally Other Name: None
Experimental: Combination Module 1: AZD7648 + PLD AZD7648 will be administered in combination with Pegylated liposomal doxorubicin (PLD)	Drug: AZD7648 Core: AZD7648 will be administered orally Other Name: None Drug: PLD The starting dose of PLD is 40 mg/m^2, administered by intravenous infusion once every 4 weeks, for a maximum of 6 cycles Other Name: DOXIL, Caelyx

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 30 patients were enrolled at two sites in the United States and three sites in the United Kingdom from 09 October 2019 to 07 December 2022.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients who met the inclusion and none of the exclusion criteria were enrolled to the study. This study consisted of a screening period of 28 days. All the study assessments were performed as per schedule of assessment.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Participant Flow for 2 periods

Period 1: Monotherapy Part A

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)
STARTED	1	1	1	1	3	4	3
COMPLETED	1	0	0	0	2	1	1
NOT COMPLETED	0	1	1	1	1	3	2
Withdrawal by Subject	0	0	0	0	1	1	0
Progressive Disease	0	1	0	0	0	1	2
Death	0	0	1	1	0	1	0

Period 2: Combination therapy Part A

	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
STARTED	2	2	5	7
COMPLETED	0	0	1	1
NOT COMPLETED	2	2	4	6
Adverse Event	0	0	1	1
Progressive disease	1	0	2	3
Death	0	1	0	1
Withdrawal by Subject	0	0	1	0
Other than specified main reasons	0	1	0	0
Physician Decision	1	0	0	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

All patients who received at least 1 dose of any study treatment.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Baseline Measures

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Total
Number of Participants [units: Participants]	1	1	1	1	3	4	3	2	2	5	7	30
Sex/Gender, Customized [units: Participants]
All	1	1	1	1	1	1	0	2	2	0	1	11
Male	0	0	0	0	2	0	0	0	0	2	0	4
Female	0	0	0	0	0	3	3	0	0	3	6	15
Race/Ethnicity, Customized [units: Participants] Race
Other	1	1	1	1	3	2	3	0	0	0	2	14
White	0	0	0	0	0	2	0	2	2	5	5	16
Age, Customized [units: Years] Mean ± Standard Deviation	NA ± NA ^[1]	NA ± NA ^[1]	NA ± NA ^[1]	NA ± NA ^[1]	64.3 ± 6.35	60.3 ± 8.18	51.3 ± 2.08	NA ± NA ^[1]	NA ± NA ^[1]	56.6 ± 10.16	61.7 ± 16.18	60.20 ± 10.20

Outcome Measures

1. Primary Outcome Measure: Number of patients with adverse events or serious adverse events [ Time Frame: From Screening (Day -28) till study drug discontinuation (3.2 years) ]

Measure Type	Primary
Measure Name	Number of patients with adverse events or serious adverse events
Measure Description	Safety and tolerability of AZD7648 when given orally to patients with advanced malignancies, as monotherapy and in combination with anti-cancer agents was assessed.
Time Frame	From Screening (Day -28) till study drug discontinuation (3.2 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	3	4	3	2	2	5	7
Number of patients with adverse events or serious adverse events [units: Participants]
Any AE	0	1	1	1	2	4	3	2	2	4	7
Any AE possibly related to AZD7648	0	0	0	0	1	2	2	2	2	4	7
Any AE possibly related to PLD								2	2	4	4
Any AE of CTCAE Grade 3 or higher	0	0	0	0	2	4	2	2	2	0	5
Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648	0	0	0	0	0	2	2	2	2	0	4
Any AE of CTCAE Grade 3 or higher, possibly related to PLD								2	2	0	1
Any AE with outcome of death	0	0	0	0	0	1	0	0	0	0	1
Any AE with outcome of death, possibly related to AZD7648	0	0	0	0	0	0	0	0	0	0	0
Any AE with outcome of death, possibly related to PLD								0	0	0	0
Any SAE	0	0	0	0	1	4	0	1	1	0	4
Any SAE, possibly related to AZD7648	0	0	0	0	0	1	0	1	0	0	2
Any SAE, possibly related to PLD								1	0	0	0
Any SAE with outcome of death	0	0	0	0	0	1	0	0	0	0	1
Any SAE with outcome of death, possibly related to AZD7648	0	0	0	0	0	0	0	0	0	0	0
Any SAE with outcome of death, possibly related to PLD								0	0	0	0
Any SAE causing discontinuation of AZD7648	0	0	0	0	0	3	0	0	0	0	0
Any SAE causing discontinuation of AZD7648, possibly related to AZD7648	0	0	0	0	0	1	0	0	0	0	0
Any SAE causing discontinuation of AZD7648, possibly related to PLD								0	0	0	0
Any AE leading to discontinuation of AZD7648	0	0	0	0	0	3	0	0	1	1	1
Any AE leading to discontinuation of PLD								0	1	1	1
Any AE leading to AZD7648 dose reduction	0	0	0	0	0	1	1	1	0	0	1
Any AE leading to PLD dose reduction								0	0	0	1
Any AE leading to AZD7648 dose interruption	0	0	0	0	1	3	2	2	2	1	4
Any AE leading to PLD dose interruption								2	1	1	4
Any AE leading to AZD7648 dose modification	0	0	0	0	1	3	2	2	2	1	5
Any AE leading to PLD dose modification								2	1	1	5

No statistical analysis provided for Number of patients with adverse events or serious adverse events

2. Primary Outcome Measure: Number of patients with dose limiting toxicities (DLTs) [ Time Frame: From Screening (Day -28) till study drug discontinuation (3.2 years) ]

Measure Type	Primary
Measure Name	Number of patients with dose limiting toxicities (DLTs)
Measure Description	A DLT is defined as an AE that occurs from the first dose of study treatment up to and including Cycle 1, Day 28 (the DLT assessment period) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications.
Time Frame	From Screening (Day -28) till study drug discontinuation (3.2 years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	3	4	3	2	2	4	7
Number of patients with dose limiting toxicities (DLTs) [units: Participants]	0	0	0	0	0	0	1	2	0	0	1

No statistical analysis provided for Number of patients with dose limiting toxicities (DLTs)

3. Secondary Outcome Measure: Area under plasma concentration-time curve from zero to infinity (AUCinf) [ Time Frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose [each cycle is 28 days] ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve from zero to infinity (AUCinf)
Measure Description	The AUCinf of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time Frame	Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose [each cycle is 28 days]
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected pharmacokinetic (PK).

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	1	3	3	2	2	4	7
Area under plasma concentration-time curve from zero to infinity (AUCinf) [units: h*nmol/L] Geometric Mean (Standard Deviation)	NA (NA)^[1]	NA (NA)^[1]	NA (NA)^[1]	NA (NA)^[1]	NA (NA)^[1]	25180 (48.76)	29680 (19.72)	NA (NA)^[1]	NA (NA)^[1]	3826 (55.72)	5539 (52.04)

No statistical analysis provided for Area under plasma concentration-time curve from zero to infinity (AUCinf)

4. Secondary Outcome Measure: Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) [ Time Frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days) ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)
Measure Description	The AUClast of AZD7648, following a single dose, when given orally as monotherapy and in combination with anti-cancer agents.
Time Frame	Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	2	3	3	2	2	4	7
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) [units: h*nmol/L] Geometric Mean (Geometric Coefficient of Variation)	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	24940 (49.04%)	29540 (19.64%)	NA (NA%)^[1]	NA (NA%)^[1]	3798 (55.78%)	5509 (52.19%)

No statistical analysis provided for Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)

5. Secondary Outcome Measure: Area under plasma concentration-time curve in the dosing interval τ (AUCτ) [ Time Frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days) ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve in the dosing interval τ (AUCτ)
Measure Description	The AUCτ of AZD7648, at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time Frame	Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
AZD7648 + PLD Dose X (Combination therapy)	Patients received single dosing of dose B of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	AZD7648 + PLD Dose X (Combination therapy)
Number of Participants Analyzed [units:participants]	1	0	1	1	0	0	0	2	1	1
Area under plasma concentration-time curve in the dosing interval τ (AUCτ) [units: h*nmol/L] Geometric Mean (Geometric Coefficient of Variation)	NA (NA%)^[1]		NA (NA%)^[1]	NA (NA%)^[1]				NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]

No statistical analysis provided for Area under plasma concentration-time curve in the dosing interval τ (AUCτ)

6. Secondary Outcome Measure: Maximum observed plasma (peak) drug concentration after single dose and multiple doses (Cmax) [ Time Frame: Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days) ]

Measure Type	Secondary
Measure Name	Maximum observed plasma (peak) drug concentration after single dose and multiple doses (Cmax)
Measure Description	The Cmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time Frame	Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	2	3	3	2	2	4	7
Maximum observed plasma (peak) drug concentration after single dose and multiple doses (Cmax) [units: nmol/L] Geometric Mean (Geometric Coefficient of Variation)
Cycle 0 Day 1	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	2463 (56.72%)	4026 (13.97%)	NA (NA%)^[1]	NA (NA%)^[1]	376.8 (27.66%)	754.2 (34.29%)
Cycle 1 Day 7 Cycle 1 Day 8	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	5426 (12.75%)	NA (NA%)^[1]		NA (NA%)^[1]	944.9 (62.85%)

No statistical analysis provided for Maximum observed plasma (peak) drug concentration after single dose and multiple doses (Cmax)

7. Secondary Outcome Measure: Time to reach maximum plasma concentration (tmax) [ Time Frame: Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days) ]

Measure Type	Secondary
Measure Name	Time to reach maximum plasma concentration (tmax)
Measure Description	The tmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time Frame	Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	2	3	3	2	2	5	7
Time to reach maximum plasma concentration (tmax) [units: Hours] Median (Full Range)
Cycle 0 Day 1	NA (1.08 to 1.08) ^[1]	NA (2.17 to 2.17) ^[1]	NA (1.00 to 1.00) ^[1]	NA (1.03 to 1.03) ^[1]	NA (2.07 to 9.00) ^[1]	2.050 (2.03 to 2.13)	2.033 (1.08 to 2.07)	NA (1.07 to 2.08) ^[1]	NA (1.08 to 2.08) ^[1]	3.058 (1.95 to 8.07)	1.150 (0.68 to 2.17)
Cycle 1 Day 7 Cycle 1 Day 8	NA (1.12 to 1.12) ^[1]	NA (2.07 to 2.07) ^[1]	NA (1.05 to 1.05) ^[1]	NA (2.00 to 2.00) ^[1]	NA (2.00 to 2.00) ^[1]	NA (2.07 to 2.15) ^[1]	2.167 (2.10 to 2.42)	NA (1.08 to 2.00) ^[1]		NA (2.03 to 2.03) ^[1]	1.100 (1.00 to 2.20)

No statistical analysis provided for Time to reach maximum plasma concentration (tmax)

8. Secondary Outcome Measure: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) [ Time Frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days) ]

Measure Type	Secondary
Measure Name	Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
Measure Description	The t½λ of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time Frame	Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	1	3	3	2	2	4	7
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) [units: Hours] Geometric Mean (Geometric Coefficient of Variation)	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	10.32 (39.41%)	10.64 (27.39%)	NA (NA%)^[1]	NA (NA%)^[1]	6.506 (44.51%)	7.562 (51.64%)

No statistical analysis provided for Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)

9. Secondary Outcome Measure: Accumulation ratio for area under curve (Rac AUC) [ Time Frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days) ]

Measure Type	Secondary
Measure Name	Accumulation ratio for area under curve (Rac AUC)
Measure Description	The Rac AUC of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Accumulation ratio for AUC, calculated by multiple dose AUCτ/single dose AUC(0-12) or AUC(0-24).
Time Frame	Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	0	1	1	0	0	0	2	1	1
Accumulation ratio for area under curve (Rac AUC) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	NA (NA%)^[1]		NA (NA%)^[1]	NA (NA%)^[1]				NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]

No statistical analysis provided for Accumulation ratio for area under curve (Rac AUC)

10. Secondary Outcome Measure: Accumulation ratio for Cmax (Rac Cmax) [ Time Frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days) ]

Measure Type	Secondary
Measure Name	Accumulation ratio for Cmax (Rac Cmax)
Measure Description	The Rac Cmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Accumulation ratio for Cmax, calculated by multiple dose Cmax/single dose Cmax.
Time Frame	Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	0	1	1	1	2	3	2	1	5
Accumulation ratio for Cmax (Rac Cmax) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	NA (NA%)^[1]		NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]	1.348 (1.272%)	NA (NA%)^[1]	NA (NA%)^[1]	1.157 (23.99%)

No statistical analysis provided for Accumulation ratio for Cmax (Rac Cmax)

11. Secondary Outcome Measure: Dose proportionality (TCP) [ Time Frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days) ]

Measure Type	Secondary
Measure Name	Dose proportionality (TCP)
Measure Description	The TCP of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Temporal change parameter in systemic exposure, calculated as multiple dose AUCtau/single dose AUCinf.
Time Frame	Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	0	1	1	0	0	0	2	1	1
Dose proportionality (TCP) [units: Ratio] Geometric Mean (Geometric Coefficient of Variation)	NA (NA%)^[1]		NA (NA%)^[1]	NA (NA%)^[1]				NA (NA%)^[1]	NA (NA%)^[1]	NA (NA%)^[1]

No statistical analysis provided for Dose proportionality (TCP)

12. Secondary Outcome Measure: Objective response rate (ORR) [ Time Frame: First dose of study treatment on Cycle 1 Day 1 (each cycle is 28 days) until progression or the last evaluable assessment in the absence of progression (3.2 years) ]

Measure Type	Secondary
Measure Name	Objective response rate (ORR)
Measure Description	ORR is defined as the percentage of patients who have a confirmed visit response of complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by Response Evaluation Criteria in Solid Tumours 1.1). CR is defined when all target lesions (TLs) and non-target lesions (NTLs) present at baseline have disappeared (with the exception of lymph nodes which must be <10mm to be considered non pathological) and no new lesions have developed since baseline. PR is defined when the sum of diameters of the TLs has decreased by 30% or more compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions.
Time Frame	First dose of study treatment on Cycle 1 Day 1 (each cycle is 28 days) until progression or the last evaluable assessment in the absence of progression (3.2 years)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Evaluable for objective response set included all patients who had a measurable baseline disease (having at least one measurable target lesion, not previously irradiated, which is ≥ 10 mm in the longest diameter (LD) (except lymph nodes which must have short axis ≥ 15 mm) by RECIST 1.1 assessment and received at least one dose of any study treatment.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	2	4	2	2	2	5	6
Objective response rate (ORR) [units: Percentage of participants]	0	0	0	0	0	0	0	0	50	0	0

No statistical analysis provided for Objective response rate (ORR)

13. Secondary Outcome Measure: Progression Free Survival (PFS) for Monotherapy [ Time Frame: At 12 months ]

Measure Type	Secondary
Measure Name	Progression Free Survival (PFS) for Monotherapy
Measure Description	PFS is defined as the time from first dose of Cycle 1 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as increased by > 20% or more compared to the smallest sum of diameters on study.
Time Frame	At 12 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Evaluable for efficacy set included all patients who received at least 1 dose of any study treatment and have a baseline tumour assessment according to RECIST 1.1.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.

Measured Values

	Cohort 1: AZD7648 Dose A (Monotherapy)	Cohort 2: AZD7648 Dose A1 (Monotherapy)	Cohort 3: AZD7648 Dose B1 (Monotherapy)	Cohort 4: AZD7648 Dose C1 (Monotherapy)	Cohort 5: AZD7648 Dose D1 (Monotherapy)	Cohort 6: AZD7648 Dose E1 (Monotherapy)	Cohort 7: AZD7648 Dose F1 (Monotherapy)
Number of Participants Analyzed [units:participants]	1	1	1	1	3	4	3
Progression Free Survival (PFS) for Monotherapy [units: Months] Median (Inter-Quartile Range)	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]	1.91 (1.71 to 3.42)	2.50 (1.64 to 3.52)	1.51 (1.05 to 7.20)

No statistical analysis provided for Progression Free Survival (PFS) for Monotherapy

14. Secondary Outcome Measure: Progression Free Survival (PFS) for Combination therapy [ Time Frame: At 18 months ]

Measure Type	Secondary
Measure Name	Progression Free Survival (PFS) for Combination therapy
Measure Description	PFS is defined as the time from first dose of Cycle 1 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as increased by > 20% or more compared to the smallest sum of diameters on study.
Time Frame	At 18 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Evaluable for efficacy set included all patients who received at least 1 dose of any study treatment and have a baseline tumour assessment according to RECIST 1.1.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Measured Values

	Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Cohort 3: AZD7648 Dose X + PLD (Combination therapy)
Number of Participants Analyzed [units:participants]	2	2	5	7
Progression Free Survival (PFS) for Combination therapy [units: Months] Median (Inter-Quartile Range)	NA (NA to NA) ^[1]	NA (NA to NA) ^[1]	1.74 (1.66 to 1.84)	2.07 (1.87 to 4.11)

No statistical analysis provided for Progression Free Survival (PFS) for Combination therapy

Serious Adverse Events

Time Frame	From Screening (Day -28) till study drug discontinuation (3.2 years)
Additional Description	No text entered.

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Serious Adverse Events

Cohort 1: AZD7648 Dose A (Monotherapy)

Cohort 2: AZD7648 Dose A1 (Monotherapy)

Cohort 3: AZD7648 Dose B1 (Monotherapy)

Cohort 4: AZD7648 Dose C1 (Monotherapy)

Cohort 5: AZD7648 Dose D1 (Monotherapy)

Cohort 6: AZD7648 Dose E1 (Monotherapy)

Cohort 7: AZD7648 Dose F1 (Monotherapy)

Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)

Cohort 1: AZD7648 Dose C + PLD (Combination therapy)

Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)

Cohort 3: AZD7648 Dose X + PLD (Combination therapy)

Total, serious adverse events

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

4/4 (100.00%)

0/3 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

4/7 (57.14%)

Infections and infestations

COVID-19¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Infections and infestations

Enterococcal sepsis¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Infections and infestations

Infection¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Hepatobiliary disorders

Biliary obstruction¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Infections and infestations

Arthritis bacterial¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Cardiac disorders

Cardiac arrest¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Vascular disorders

Embolism¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Vascular disorders

Hypotension¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Gastrointestinal disorders

Stomatitis¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Investigations

Neutrophil count decreased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Injury, poisoning and procedural complications

Fall¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Injury, poisoning and procedural complications

Femur fracture¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Injury, poisoning and procedural complications

Hip fracture¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Injury, poisoning and procedural complications

Post procedural pulmonary embolism¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Infections and infestations

Urosepsis¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 25.1

Other Adverse Events

Time Frame	From Screening (Day -28) till study drug discontinuation (3.2 years)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Cohort 1: AZD7648 Dose A (Monotherapy)	Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 2: AZD7648 Dose A1 (Monotherapy)	Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 3: AZD7648 Dose B1 (Monotherapy)	Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 4: AZD7648 Dose C1 (Monotherapy)	Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 5: AZD7648 Dose D1 (Monotherapy)	Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 6: AZD7648 Dose E1 (Monotherapy)	Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 7: AZD7648 Dose F1 (Monotherapy)	Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach.
Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)	Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by intravenous (IV) infusion once every 4 weeks.
Cohort 1: AZD7648 Dose C + PLD (Combination therapy)	Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)	Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.
Cohort 3: AZD7648 Dose X + PLD (Combination therapy)	Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m^2, administered by IV infusion once every 4 weeks.

Other Adverse Events

Cohort 1: AZD7648 Dose A (Monotherapy)

Cohort 2: AZD7648 Dose A1 (Monotherapy)

Cohort 3: AZD7648 Dose B1 (Monotherapy)

Cohort 4: AZD7648 Dose C1 (Monotherapy)

Cohort 5: AZD7648 Dose D1 (Monotherapy)

Cohort 6: AZD7648 Dose E1 (Monotherapy)

Cohort 7: AZD7648 Dose F1 (Monotherapy)

Cohort 1: AZD7648 Dose C1 + PLD (Combination therapy)

Cohort 1: AZD7648 Dose C + PLD (Combination therapy)

Cohort 2: AZD7648 Dose C2 + PLD (Combination therapy)

Cohort 3: AZD7648 Dose X + PLD (Combination therapy)

Total, other (not including serious) adverse events

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

2/3 (66.67%)

4/4 (100.00%)

3/3 (100.00%)

2/2 (100.00%)

4/5 (80.00%)

7/7 (100.00%)

Infections and infestations

COVID-19¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Infections and infestations

Lower respiratory tract infection¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

2/7 (28.57%)

# events

Infections and infestations

Upper respiratory tract infection¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Infections and infestations

Urinary tract infection¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

2/5 (40.00%)

1/7 (14.29%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour pain¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

0/1 (0.00%)

2/3 (66.67%)

1/4 (25.00%)

1/3 (33.33%)

1/2 (50.00%)

2/5 (40.00%)

7/7 (100.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

1/3 (33.33%)

2/2 (100.00%)

0/2 (0.00%)

0/5 (0.00%)

3/7 (42.86%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

2/2 (100.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/1 (0.00%)

2/3 (66.67%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/5 (20.00%)

3/7 (42.86%)

# events

Metabolism and nutrition disorders

Dehydration¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Metabolism and nutrition disorders

Hypoalbuminaemia¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Metabolism and nutrition disorders

Hyponatraemia¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Metabolism and nutrition disorders

Hypophosphataemia¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Nervous system disorders

Dizziness¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

1/5 (20.00%)

0/7 (0.00%)

# events

Eye disorders

Visual impairment¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Cardiac disorders

Pericardial effusion¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Vascular disorders

Hypotension¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Vascular disorders

Lymphoedema¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Vascular disorders

Vena cava thrombosis¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Productive cough¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Upper-airway cough syndrome¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

2/3 (66.67%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Ascites¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

2/7 (28.57%)

# events

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/1 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

1/3 (33.33%)

0/2 (0.00%)

1/2 (50.00%)

1/5 (20.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Duodenal ulcer¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Hypoaesthesia oral¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Lip swelling¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Mouth ulceration¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

0/1 (0.00%)

2/3 (66.67%)

1/4 (25.00%)

1/3 (33.33%)

0/2 (0.00%)

1/2 (50.00%)

2/5 (40.00%)

4/7 (57.14%)

# events

Gastrointestinal disorders

Obstruction gastric¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Stomatitis¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

2/2 (100.00%)

1/2 (50.00%)

2/5 (40.00%)

2/7 (28.57%)

# events

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

2/4 (50.00%)

1/3 (33.33%)

0/2 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dry skin¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Skin and subcutaneous tissue disorders

Night sweats¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

1/5 (20.00%)

0/7 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash maculo-papular¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

1/3 (33.33%)

1/2 (50.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

General disorders

Fatigue¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/1 (0.00%)

1/3 (33.33%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

2/2 (100.00%)

3/5 (60.00%)

3/7 (42.86%)

# events

General disorders

Non-cardiac chest pain¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

General disorders

Oedema peripheral¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

General disorders

Pyrexia¹

# participants affected / at risk

0/1 (0.00%)

1/1 (100.00%)

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Investigations

Aspartate aminotransferase increased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Investigations

Blood alkaline phosphatase increased¹

# participants affected / at risk

0/1 (0.00%)

1/3 (33.33%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Investigations

Blood bilirubin increased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Investigations

Blood creatinine increased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Investigations

Gamma-glutamyltransferase increased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Investigations

Weight decreased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

1/4 (25.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Injury, poisoning and procedural complications

Procedural pain¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

1/3 (33.33%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Infections and infestations

Candida infection¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Infections and infestations

Cellulitis¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Infections and infestations

Groin abscess¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Infections and infestations

Oral candidiasis¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

2/7 (28.57%)

# events

Infections and infestations

Pleural infection¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Blood and lymphatic system disorders

Leukopenia¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Metabolism and nutrition disorders

Hyperlipidaemia¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Metabolism and nutrition disorders

Hypernatraemia¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Nervous system disorders

Hypoaesthesia¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Nervous system disorders

Neuralgia¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Ear and labyrinth disorders

External ear pain¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Cardiac disorders

Angina pectoris¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Cardiac disorders

Atrial flutter¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Vascular disorders

Hypertension¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Vascular disorders

Thrombophlebitis¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea exertional¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/5 (20.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Abdominal distension¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Gastrointestinal disorders

Abdominal pain upper¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/5 (20.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Eructation¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Gastrointestinal disorders

Oesophagitis¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Oral pain¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Gastrointestinal disorders

Pancreatitis¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Gastrointestinal disorders

Toothache¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Skin and subcutaneous tissue disorders

Decubitus ulcer¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis contact¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Skin and subcutaneous tissue disorders

Palmar-plantar erythrodysaesthesia syndrome¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash erythematous¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pathological fracture¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Renal and urinary disorders

Haematuria¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/5 (20.00%)

0/7 (0.00%)

# events

Renal and urinary disorders

Micturition urgency¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

1/5 (20.00%)

0/7 (0.00%)

# events

Reproductive system and breast disorders

Pelvic pain¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Reproductive system and breast disorders

Testicular oedema¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

General disorders

Catheter site pain¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

General disorders

Mucosal inflammation¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

General disorders

Pain¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

General disorders

Peripheral swelling¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Investigations

Neutrophil count decreased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

0/2 (0.00%)

2/2 (100.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Investigations

Platelet count decreased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

2/2 (100.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Investigations

White blood cell count decreased¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/5 (0.00%)

1/7 (14.29%)

# events

Injury, poisoning and procedural complications

Infusion related reaction¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

1/5 (20.00%)

1/7 (14.29%)

# events

Injury, poisoning and procedural complications

Sunburn¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

Cardiac disorders

Atrial fibrillation¹

# participants affected / at risk

0/1 (0.00%)

0/3 (0.00%)

0/4 (0.00%)

0/3 (0.00%)

1/2 (50.00%)

0/2 (0.00%)

0/5 (0.00%)

0/7 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 25.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Protocol redacted
Download
SAP redacted
Download
CSR Synopsis redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Dr Timothy Yap

MD Anderson Cancer Center, 1400 Holcombe Blvd. Houston, Texas, 77030

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Protocol redacted

SAP redacted

CSR Synopsis redacted

Trial Results Summaries