Efficacy and Safety of Neoadjuvant Olaparib Monotherapy and Olaparib PlusDurvalumab Combination in HER2-Negative BRCAm Breast Cancer

Phase 1

• Conditions: BRCA Mutations and Early Stage HER2-Negative Breast Cancer; MedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-005231-22-AT
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-11
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 50

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, non-metastatic 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 core needle 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.

For a complete overview of the inclusion criteria refer to the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

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

For a complete overview of the exclusion criteria refer to the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified