Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer
Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B/OPERETTA)
1 other identifier
interventional
23
1 country
3
Brief Summary
This is a Phase II, single-arm, open label study to evaluate Olaparib plus Pembrolizumab following platinum-based chemotherapy plus Pembrolizumab as neoadjuvant therapy for germline BRCA (gBRCA) 1/2 mutated triple negative breast cancer (TNBC). Pembrolizumab in combination with weekly paclitaxel and carboplatin (treatment 1) is followed by Pembrolizumab in combination with Olaparib (treatment 2) in neoadjuvant setting and Pembrolizumab in combination with Olaparib in adjuvant setting will be studied
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jul 2024
Typical duration for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 1, 2022
CompletedFirst Posted
Study publicly available on registry
August 3, 2022
CompletedStudy Start
First participant enrolled
July 16, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2028
March 20, 2025
January 1, 2025
4 years
August 1, 2022
March 17, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Pathological Complete Response (pCR) Rate (ypT0/TisypN0)
Pathological complete response rate (ypT0/TisypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.
From 27 weeks up to 30 weeks
Secondary Outcomes (7)
Residual Cancer Burden 0/1
From 27 weeks up to 30 weeks
Pathological Complete Response (pCR) Rate (ypT0/is)
From 27 weeks up to 30 weeks
Pathological Complete Response (pCR) Rate (ypT0/Tis ypN0)
From 27 weeks Up to 30 weeks
Three-Year Overall Survival (3-year OS)
Up to 3 years
Three-Year Distant Metastatic Free Survival (3-year DMFS)
Up to 3 years
- +2 more secondary outcomes
Study Arms (1)
Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib
EXPERIMENTAL1. Neoadjuvant phase; Treatment 1: Pembrolizumab+ Paclitaxel + Carboplatin (Cycles 1-4) Treatment 2: Pembrolizumab + Olaparib (Cycles 1-4) 2. Definitive Surgery 3. Adjuvant phase; Pembrolizumab + Olaparib (1-9 cycles) Note: each cycle = 3 weeks (Neoadjuvant Treatment 1 and 2, and Adjuvant Treatment)
Interventions
200 mg fixed dose, IV, every 3 weeks (Q3W), on Days 1 of Cycles 1-4
80 mg/m2, IV, weekly, on Days 1, 8, 15 of Cycles 1-4
Area under the curve (AUC 1.5), intravenously (IV), weekly, on Days 1, 8, 15 of Cycles 1-4
300 mg BID (twice daily) orally
Each subject will undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant treatment.
Eligibility Criteria
You may qualify if:
- Male/female subjects who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of invasive breast cancer
- Have histologically confirmed TNBC, as defined by the most recent ASCO/CAP guidelines.
- Confirmed germline BRCA 1/2 mutated.
- Have previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per AJCC for breast cancer staging criteria version 7 as assessed by the investigator based on radiological and/or clinical assessment:
- T1c, N1-N2
- T2, N0-N2
- T3, N0-N2
- T4a-d, N0-N2
- It has been confirmed that there is no distant metastasis to each organ by the following tests. Chest: Contrast CT or FDG-PET/CT Abdominal: Contract CT\* or FDG-PET/CT Bone: Bone scintigraphy or FDG-PET/CT Brain: In the case of no central nervous system symptoms, examination for brain metastasis is not required.
- The subject (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of study treatment.
You may not qualify if:
- Subjects who has a positive urine pregnancy test within 72 hours prior to registration
- Has diagnosed as inflammatory breast cancer.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor .
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and investigational drugs used in this study and/or any of their excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years
- Has a history of (non-infectious) pneumonitis/interstitial lung disease .
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HbsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Okayama Universitylead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (3)
Gifu University Hospital
Gifu, Gifu, 5011194, Japan
Okayama University Hospital
Okayama, Japan
St. Luke's International Hospital
Tokyo, Japan
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yuko Takahashi, MD., PhD.
Assistant Professor, Endocrinological Center, Okayama University Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant professor, Endocrinological Center
Study Record Dates
First Submitted
August 1, 2022
First Posted
August 3, 2022
Study Start
July 16, 2024
Primary Completion (Estimated)
June 30, 2028
Study Completion (Estimated)
September 30, 2028
Last Updated
March 20, 2025
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will not share