Triple Negative Breast NeoplasmsPhase 2NCT05485766
Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer
A Phase 2 study testing Pembrolizumab, Paclitaxel and Carboplatin in people with Triple Negative Breast Neoplasms and Triple Negative Breast Cancer, run by Okayama University at 3 sites in Japan.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Neoplasms, Triple Negative Breast Cancer, Breast Neoplasms
- What is being tested?
- Pembrolizumab, Paclitaxel and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 3 sitesJapan
- Study dates
- 16 Jul 2024to 30 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Show all 28Show fewer
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children.
- Has had an allogenic tissue/solid organ transplant.
- Has received pre-treatment with Olaparib or other PARP inhibitors.
- Has significant cardiovascular disease
- Has a resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions.
- Subject has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
- Subject received colony-stimulating factors within 28 days prior to the first dose of study intervention.
- Subject is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
- Is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption.
- Is, in the judgement of the investigator, unlikely to comply with the study procedures, restrictions, and requirements of the study.
- Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study.
- Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Japan3 sites, 3 recruiting
- Recruiting
Gifu University Hospital
Gifu, Gifu, 5011194
Manabu Futamura, MD., PhD., +81-58-230-6000
Manabu Futamura, MD., PhD.
- Recruiting
Okayama University Hospital
Okayama
Yuko Takahashi, MD., PhD.
- Recruiting
St. Luke's International Hospital
Tokyo
Kumiko Kida, MD., PhD.
About this study
Official title: Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B/OPERETTA)
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
- Conditions
- Triple Negative Breast Neoplasms, Triple Negative Breast Cancer, Breast Neoplasms, Breast Cancer, BRCA1 Mutation, BRCA2 Mutation
- Being tested
- Pembrolizumab, Paclitaxel, Carboplatin, Olaparib, Definitive Surgery
- Keywords
- BRCA1 protein, BRCA2 protein
- Medical subject headings
- Triple Negative Breast Neoplasms, Breast Neoplasms, Fanconi Anemia, Complementation Group D1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda, MK-3475
200 mg fixed dose, IV, every 3 weeks (Q3W), on Days 1 of Cycles 1-4
PaclitaxelDrug
80 mg/m2, IV, weekly, on Days 1, 8, 15 of Cycles 1-4
CarboplatinDrug
Area under the curve (AUC 1.5), intravenously (IV), weekly, on Days 1, 8, 15 of Cycles 1-4
OlaparibDrug
Also called Lynparza
300 mg BID (twice daily) orally
Definitive SurgeryProcedure or surgery
Each subject will undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant treatment.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib | Experimental | 1. 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) Receives: Drug: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin; Drug: Olaparib; Procedure: Definitive Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From 27 weeks up to 30 weeks
Secondary outcomes (7)
Residual Cancer Burden 0/1
Residual Cancer Burden (RCB) 0/1 rate is defined as the proportion of subjects on evaluation from routine pathologic sections of the primary breast tumor and the regional lymph nodes after the completion of neoadjuvant therapy assessed by the local pathologist at the time of definitive surgery. Six variables are included in a calculation formula. The calculated RCB index value can also be categorized as one of four RCB classes (0 - 3). The calculation formula and detailed description can be found at a dedicated Web site: http://www.mdanderson.org/breastcancer_RCB.
Measured: From 27 weeks up to 30 weeks
Pathological Complete Response (pCR) Rate (ypT0/is)
Pathological complete response rate (ypT0/is) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen regardless of regional lymph nodes status following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.
Measured: From 27 weeks up to 30 weeks
Pathological Complete Response (pCR) Rate (ypT0/Tis ypN0)
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.
Measured: From 27 weeks Up to 30 weeks
Three-Year Overall Survival (3-year OS)
The Proportion of Three Year-Overall Survival (3y-OS) is defined as the proportion of survival subjects without death due to any cause at 3 years from registration. Subjects without documented death at the time of the analysis will be censored at the date of the last follow-up.
Measured: Up to 3 years
Three-Year Distant Metastatic Free Survival (3-year DMFS)
The Proportion of Three-Year Distant Metastatic Free Survival (3y-DMFS) is defined as the proportion of survival subjects without distant metastatic disease at 3 years from registration. Subjects without documented distant metastatic disease at the time of the analysis will be censored at the date of the last follow-up.
Measured: Up to 3 years
Three-Year Disease Free Survival (3-year DFS)
The Proportion of Three-Year Disease Free Survival (3y-DFS) is defined as the proportion of survival subjects without metastatic disease and secondary malignancy at 3 years from registration. Subjects without documented metastatic disease and secondary malignancy at the time of the analysis will be censored at the date of the last follow-up.
Measured: Up to 3 years
AEs/SAEs and treatment discontinuation due to AEs/SAEs
Safety measurements are the incidence of, causality of, and outcome of AEs/SAEs; and changes in vital sign measurements and laboratory values.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2022
- Study start16 Jul 2024
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Okayama University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Yuko Takahashi, Okayama University
- Investigators
- Yuko Takahashi, MD., PhD., Principal investigator, Assistant Professor, Endocrinological Center, Okayama University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05485766
- Sponsor's protocol ID
- OUMK59829
- Status last verified
- Jan 2025
- First submitted
- 1 Aug 2022
- Last updated
- 20 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B/OPERETTA)
- ClinicalTrials.gov ID
- NCT05485766
- Acronym / sponsor ID
- OUMK59829
- Conditions
- Triple Negative Breast Neoplasms, Triple Negative Breast Cancer, Breast Neoplasms, Breast Cancer, BRCA1 Mutation, BRCA2 Mutation
- Keywords
- BRCA1 protein, BRCA2 protein
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 23 participants (estimated)
- Lead sponsor
- Okayama UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 16 Jul 2024 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 3 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib | Experimental | Drug: Pembrolizumab, Drug: Paclitaxel, Drug: Carboplatin, Drug: Olaparib, Procedure: Definitive Surgery1. 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- 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.
Key exclusion criteria (28 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: Keytruda, MK-3475200 mg fixed dose, IV, every 3 weeks (Q3W), on Days 1 of Cycles 1-4 | Drug | Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib |
| Paclitaxel80 mg/m2, IV, weekly, on Days 1, 8, 15 of Cycles 1-4 | Drug | Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib |
| CarboplatinArea under the curve (AUC 1.5), intravenously (IV), weekly, on Days 1, 8, 15 of Cycles 1-4 | Drug | Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib |
| OlaparibAlso: Lynparza300 mg BID (twice daily) orally | Drug | Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib |
| Definitive SurgeryEach subject will undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant treatment. | Procedure or surgery | Pembrolizumab+ Paclitaxel + Carboplatin Followed by Pembrolizumab + Olaparib |
Primary outcome
Pathological Complete Response (pCR) Rate (ypT0/TisypN0)
Time frame: From 27 weeks up to 30 weeks
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.
7 secondary outcomes
Residual Cancer Burden 0/1
Time frame: From 27 weeks up to 30 weeks
Pathological Complete Response (pCR) Rate (ypT0/is)
Time frame: From 27 weeks up to 30 weeks
Pathological Complete Response (pCR) Rate (ypT0/Tis ypN0)
Time frame: From 27 weeks Up to 30 weeks
Three-Year Overall Survival (3-year OS)
Time frame: Up to 3 years
Three-Year Distant Metastatic Free Survival (3-year DMFS)
Time frame: Up to 3 years
Three-Year Disease Free Survival (3-year DFS)
Time frame: Up to 3 years
AEs/SAEs and treatment discontinuation due to AEs/SAEs
Time frame: Up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
- Individual participant dataSharing planned: No
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Triple Negative Breast Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yuko Takahashi, MD., PhD. principal investigator
Assistant Professor, Endocrinological Center, Okayama University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Paclitaxel and Carboplatin in people with Triple Negative Breast Neoplasms and Triple Negative Breast Cancer, run by Okayama University at 3 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yuko Takahashi, MD., PhD. (+81-86-223-7151, yukotaka@okayama-u.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological Complete Response (pCR) Rate (ypT0/TisypN0) (time frame: From 27 weeks up to 30 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025.