A Phase I Study of MEDI9447 (Oleclumab) in Japanese Participants

Study identifier:D6070C00006

ClinicalTrials.gov identifier:NCT03736473

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of MEDI9447 (Oleclumab) in Japanese Patients with Advanced Solid Malignancies

Medical condition

Advanced solid malignancies

Phase

Phase 1

Healthy volunteers

Study drug

MEDI9447

Sex

All

Actual Enrollment

Study type

Interventional

Age

20 Years - 130 Years

Date

Study Start Date: 07 Nov 2018

Primary Completion Date: 19 Jun 2019

Study Completion Date: 19 Jun 2019

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Other

Verification:

Verified 01 Nov 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Adult participants; age ≥ 20 years.
- Has a histologically confirmed solid malignancy that is refractory to standard therapy or for which no standard of care regimen currently exists.
- Participants must have at least 1 lesion that is measurable using response evaluation criteria in solid tumors (RECIST) v1.1.
- All participants must consent to provide archived tumor specimens for biomarker studies.
- Eastern cooperative oncology group (ECOG) performance Status of 0 or 1.
- Life expectancy >=12 weeks
- Adequate organ function
- Body weight >= 35 kg
Major

Exclusion Criteria

- Participants must have completed any previous cancer-related treatments before enrollment.
- Prior treatment with CD73 antagonist, tumor necrosis factor receptor superfamily agonists.
- All cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1), or programmed cell death protein ligand-1 (PD-L1) antagonists related-adverse events (AEs) must have resolved to =< National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v4.03 Grade 1 or baseline prior to screening and not worsened before the first dose of study drug.
- Must not have required the use of additional immunosuppression other than corticosteroids for the management of an CTLA-4, PD-1, or PD-L1 related AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.
- Known allergy or hypersensitivity to the study drug, its compounds, or agents similar biologic composition.
- History of more than one event of IRR requiring permanent discontinuation of intravenous (IV) drug treatment.
- History of severe drug allergies or anaphylaxis to 2 or more food products or medicine.
- Cardiac or peripheral vascular disease.
- National cancer institute CTCAE v4.03 Grade 3 or greater edema.
- Uncontrolled massive ascites or pleural effusion.
- History of NCI CTCAE v4.03 Grade 3 or greater thromboembolic events within 3 months prior to the first dose of study drug or thromboembolic event of any grade with ongoing symptoms.
- Active tuberculosis.
- Participants with history of, or current interstitial lung disease (ILD).
- Active or prior documented autoimmune within the past 3 years prior to the start of treatment.
- Untreated or unstable central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression.
- Concurrent enrollment in another clinical study.
- Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
- Toxicities from prior anticancer therapy that have not resolved to ≤ NCI CTCAE v4.03 Grade 1 or baseline prior to the first dose of study drug.
- History of primary immunodeficiency or solid organ transplantation.
- Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- Females who are pregnant, lactating, or intend to become pregnant during their participation in the study.
- Other invasive malignancy within 2 years prior to the first dose of study drug.
- Uncontrolled concomitant illness.
- Judgment by the Investigator that the participant is unsuitable to participate in the study and the participant is unlikely to comply with study procedures, restrictions, and requirements.
- Involvement in the planning and/or conduct of the study.

Objectives: Primary objective: To assess the safety and tolerability, describe any dose-limiting toxicity (DLT) for MEDI9447 Secondary objective: To determine the pharmacokinetics (PK) characteristics of MEDI9447 To determine the immunogenicity of MEDI9447 To evaluate candidate biomarker of MEDI9447 activity in archival tumor biopsy specimens To describe the preliminary antitumor activity of MEDI9447 Exploratory Objective: To explore profile of biomarker status, with MEDI9447 treatment Overall design: This is a phase I, open-label study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of MEDI9447 in Japanese participants with advanced solid malignancies. This study consists of 2 cohorts. Cohort 1 (MEDI9447 Dose 1) and Cohort 2 (MEDI9447 Dose 2). At least 3 or up to 6 evaluable Japanese participants with advanced solid malignancies will be enrolled in each cohort. The total number of participants will depend upon the available data in each cohort and Safety Review Committee (SRC)’s decision. Study Period: The study is expected to start in October 2018 and end in July 2019. Number of Participants: Maximum 12 evaluable participants will be enrolled in this study. Treatments and treatment duration: Participants will receive MEDI9447 on Day 1 and Day 15 in a 4-week cycle. Participants participating in the study may continue to receive study treatment(s) as long as they are continuing to show clinical benefit, as judged by the Investigator, unless the participant has progressive disease (PD) with either clinical deterioration and/or no further benefit from treatment, experiences unacceptable toxicity, or should discontinue for any other reason. In such cases, the Investigator needs to consult with the sponsor and they agree to continue study treatment in advance. Statistical methods: The primary objective of this study is to assess the safety and tolerability profile of MEDI9447. All safety data will be summarized using the safety analysis set (All participants who received at least 1 dose of MEDI9447). Evaluations of safety and tolerability will include, but not be limited to, AEs, physical examinations, laboratory findings (including clinical chemistry, hematology, and urinalysis), vital signs (including blood pressure and pulse), and electrocardiograms using summary statistics. For secondary and exploratory efficacy endpoints, all analyses will be descriptive, and no formal statistical testing will be performed. Data will be summarized and plotted appropriately according to data type. PK concentration data for MEDI9447 will be listed for each participant and each dosing day, and summary statistics will be tabulated. Immunogenicity results will be listed by participant, and summaries of the number and percentage of participants who develop detectable antidrug antibodies (ADAs) against MEDI9447 will be provided. The immunogenicity titre will be listed for samples confirmed positive for the presence of ADAs. Neutralizing ADAs may be reported for samples confirmed positive for the presence of ADAs. All analyses and reporting will be conducted for each cohort.

No locations available

Arms	Assigned Interventions
Experimental: Cohort 1 - MEDI9447 Dose 1 Participants will receive intravenous (IV) infusion of Dose 1 of MEDI9447 every 2 weeks (Q2W) until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurrs first.	Drug: MEDI9447 Participants will receive IV infusion of Dose 1 or Dose 2 of MEDI9447 Q2W in Cohort 1 - MEDI9447 Dose 1 or Cohort 2 - MEDI9447 Dose 2. Other Name: Oleclumab
Experimental: Cohort 2 - MEDI9447 Dose 2 Participants will receive IV infusion of Dose 2 of MEDI9447 Q2W until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, or development of other reason for treatment discontinuation, whichever occurrs first.	Drug: MEDI9447 Participants will receive IV infusion of Dose 1 or Dose 2 of MEDI9447 Q2W in Cohort 1 - MEDI9447 Dose 1 or Cohort 2 - MEDI9447 Dose 2. Other Name: Oleclumab

Documents available

CSP-v3_Redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]