Study of Neoadjuvant Olaparib Monotherapy and Olaparib and Durvalumab Combination in HER2 Negative BRCAm Breast Cancer - OlympiaN

Study identifier:D931CC00001

ClinicalTrials.gov identifier:NCT05498155

EudraCT identifier:2021-005231-22

CTIS identifier:2023-503529-20-00

Recruitment Complete

Official Title

A Phase II, Multicentre, Open-Label Study to Assess the Efficacy and Safety of Olaparib Monotherapy and Olaparib Plus Durvalumab Combination as Neoadjuvant Therapy in Patients with BRCA Mutations and Early Stage HER2-Negative Breast Cancer

Medical condition

Breast Cancer

Phase

Phase 2

Healthy volunteers

Study drug

Neoadjuvant Olaparib monotherapy group, Neoadjuvant combination therapy with olaparib plus durvalumab

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 07 Nov 2022

Estimated Primary Completion Date: 20 Nov 2024

Estimated Study Completion Date: 31 Dec 2026

Study design

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

Verification:

Verified 01 Oct 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Males or Females ≥18 years
- Minimum body weight of 30 kg
- Capable of giving signed informed consent.
- Male and Female participants of childbearing potential must use effective methods of contraception
- Histologically confirmed, newly diagnosed, primary, operable, nonmetastatic invasive breast cancer with the following characteristics:
--ER-negative or ER-low defined as IHC nuclear staining ≤10%
- HER2-negative (not eligible for anti-HER2 therapy) defined as:
-- IHC 0, 1+ without in situ hybridization OR
-- In situ hybridization non-amplified with ratio less than 2.0 OR
-- In situ hybridization average HER2 copy number < 6 signals/cells
- Clinical TNM staging (per AJCC 8th Edition) as follows:
-- T1b (>5 mm but ≤10 mm), N0, no known metastases (M0 or MX); OR
-- T1c (>10 mm but ≤20 mm), N0, no known metastases (M0 or MX); OR
-- T1 (>1 mm but ≤20 mm), N1, no known metastases (M0 or MX); OR
-- T2 (>20 mm but ≤50 mm), N0, no known metastases (M0 or MX).).
- Documented deleterious or suspected deleterious mutation in BRCA1 or BRCA2 from local BRCA testing using either a germline or tumour test.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Participants must have adequate organ and bone marrow function
- Participant must be willing to undergo a baseline research biopsy prior to start of study
treatment.
- Participant must be willing to have any leftover tumour tissue/FFPE from the diagnostic
biopsy submitted for research purposes, if available.

Exclusion Criteria

- Any evidence of other diseases (such as severe or uncontrolled systemic diseases or active, uncontrolled infections, including but not
limited to, uncontrolled ventricular arrhythmia, uncontrolled hypertension, recent [within 3 months] myocardial infarction, uncontrolled major seizure disorder, renal transplant, active bleeding diseases, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography scan
- Refractory nausea and vomiting, chronic gastrointestinal disease likely to interfere with absorption of the study medication, inability to swallow the formulated product
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease for ≥5 years before the first dose of study intervention and of low potential risk for recurrence
- Participants with MDS or AML
- For higher risk (Cohort B) participants only: Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,
hypophysitis, uveitis, etc), autoimmune pneumonitis, and autoimmune myocarditis
- Known active hepatitis infection, positive hepatitis C antibody, hepatitis
B virus surface antigen or hepatitis B virus core antibody
- Known to have tested positive for human immunodeficiency virus unless currently on effective anti-retroviral therapy with an undetectable viral load within 6 months
- History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
- Participant must not have had any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation, or experimental therapy
- For higher risk (Cohort B) participants only: Prior exposure to anti-PD1, anti-PD-L1, or
anti-CTLA4 agents (ICIs); OR an agent directed to other co-inhibitory or co-stimulatory T-cell receptors
- Any concurrent anticancer treatment
- Major surgical procedure (excluding placement of vascular access, local surgery of isolated lesions, or diagnostic staging) within 2 weeks of the first dose of study intervention
- For higher risk (Cohort B) participants only: Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
- Concomitant use of:
-- Known strong cytochrome P450 (CYP3A) inhibitors or moderate
CYP3A inhibitors within 2 weeks prior to first dose of study intervention
-- Known strong CYP3A inducers or moderate CYP3A inducers .The required washout period prior to starting study therapy is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents

No locations available

Arms	Assigned Interventions
Experimental: Cohort A Cohort A will consist of a lower-risk population of participants with HER2-negative ER-negative or ER-low defined as having a tumour size >5 mm and ≤20 mm and N0 (T1b-c/N0).	Drug: Neoadjuvant Olaparib monotherapy group Neoadjuvant olaparib monotherapy (300 mg BID) for four to six 28-day cycles. Other Name: Cohort A
Experimental: Cohort B Cohort B will consist of a higher-risk population of participants with HER2-negative ER-negative or ER-low defined as having a tumour size of >20 mm but ≤50 mm and N0 (T2/N0), or having a tumour size of >1 mm but ≤20 mm and N1 (T1/N1).	Combination Product: Neoadjuvant combination therapy with olaparib plus durvalumab Neoadjuvant combination therapy with olaparib (300 mg BID) plus durvalumab (1500 mg IV Q4W) for four to six 28-day cycles. Other Name: Cohort B

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Anitra Fielding

AstraZeneca