Breast CancerPhase 2NCT03025035
Pembrolizumab in Combination With Olaparib in Advanced BRCA-mutated or HDR-defect Breast Cancer
A Phase 2 study testing Pembrolizumab and Olaparib in people with Breast Cancer, run by Yuan Yuan at 1 site in United States.
Trial summary
This trial will evaluate the use of immunotherapy and PARP inhibition in a population with incurable advanced breast cancer associated with a germline BRCA mutation or HDR-defect. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Pembrolizumab and Olaparib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Sep 2017to 21 Nov 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Be willing and able to provide written informed consent/assent for the trial
- Be ≥18 years of age on day of signing informed consent
- Advanced BRCA-mutated and/or HDR-defect breast cancer progressing on or after prior therapy for metastatic disease or locally advanced disease; Prior therapy is defined as follows: for triple negative breast cancer - progressing after at least 1 line of any prior chemotherapy; for HER2 positive disease must have progressed after at least two HER2 directed therapies in the metastatic setting including ado-trastuzumab emtansine (T-DM1); for hormone receptor positive disease (ER, PR, or both) must have progressed after a CDK4/CDK6 inhibitor plus hormonal therapy. Patients with progression within 12 months from previous neoadjuvant or adjuvant treatment could be enrolled in the study as 1st line therapy in metastatic setting.
- Measurable disease by RECIST 1.1, with at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements. Patients with non-measurable bone metastases in addition to measurable disease are eligible; however patients with non-measurable bone disease as the only site(s) of disease are not eligible.
- ECOG 0 or 1
- Documented BRCA deleterious germline or somatic mutation and/or HDR-defect.
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- FFPE tumor tissue available for analysis
- Adequate organ function
- Female subjects: Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:
- Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
- radiation-induced oophorectomy with last menses >1 year ago
- chemotherapy-induced menopause with >1 year interval since last menses
- surgical sterilization (bilateral oophorectomy or hysterectomy)
- Women of childbearing potential and their partners, who are sexually active, must agree to the use of TWO highly effective forms of contraception in combination. This should be started from the signing of the informed consent and continue throughout the period of taking study treatment and for at least 1 month after last dose of study drug(s), or they must totally/truly abstain from any form of sexual intercourse.
- Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential
- Patients must have a life expectancy ≥ 16 weeks
Who cannot join
- Is currently participating or has participated in a study of investigational agent or using an investigational device with 30 days of the first dose of pembrolizumab.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1.
- Subjects must have recovered (i.e., ≤ Grade 1 or at baseline) from any adverse events due to a previously administered agent. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Is receiving systemic steroid therapy within three days prior to the first dose of pembrolizumab or receiving any other form of immunosuppressive medication
- Is expected to require any other form of systemic or localized antineoplastic therapy while on trial.
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- Subjects with ER+/PR+ disease may be given endocrine therapy.
- Subjects with HER2+ disease will be required to discontinue trastuzumab (Herceptin).
- Has participated in another MK03475 trial.
- Note: Patients with or without prior PARP-inhibitor exposure may be included.
- Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
- Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
- Has known hypersensitivity to pembrolizumab or any of its excipients
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of pembrolizumab and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are using no steroids for at least three days prior to study medication.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis
- Has active tuberculosis
- Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
- Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
- Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of pembrolizumab. Administration of killed vaccines is allowed.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects that require inhaled steroid or local steroid injections will not be excluded from the study. Subjects with hypothyroidism not from autoimmune disease and stable on hormone replacement will not be excluded from the study. Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has had an allogenic tissue / solid organ transplant.
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
- 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 within the projected duration of the trial, starting with the screening visit (Visit 1) through 120 days after the last dose of study treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: Open Label, Phase II Pilot Study of Immune Checkpoint Inhibition With Pembrolizumab in Combination With PARP Inhibition With Olaparib in Advanced BRCA-mutated or HDR-defect Breast Cancers
This trial will evaluate the use of immunotherapy and PARP inhibition in a population with incurable advanced breast cancer associated with a germline BRCA mutation or HDR-defect. The main objective is to examine overall response rate of pembrolizumab (immunotherapy) in combination with Olaparib (PARP inhibitor) in advanced BRCA-mutated or Homology-directed repair (HDR)-defect breast cancer.
Read the detailed description
There are two BRCA genes, BRCA1 and BRCA2, and they play a role in protecting cells from cancer. HDR-defect is another type of gene mutation that can contribute to development and progression of cancer. If one of these genes is mutated, cells may rapidly change and divide, which can lead to cancer. Pembrolizumab is a drug that works with the immune system to target the tumor (immunotherapy). The investigators want to know if combining pembrolizumab and Olaparib therapy will be able to reduce the size and amount of cancer cells with fewer side effects than standard treatment by targeting the tumor. This research study is designed to test the investigational use of pembrolizumab and Olaparib in breast cancer.
- Conditions
- Breast Cancer
- Being tested
- Pembrolizumab, Olaparib
- Keywords
- BRCA-mutation, Immune checkpoint inhibition, Immunotherapy, Advanced BRCA-mutated breast cancer, HDR-defect, PARP inhibitor
- Medical subject headings
- Breast Neoplasms
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
Pembrolizumab IV solution administered on Day 1 of each 3-week cycle
OlaparibDrug
Also called Lynparza
Olaparib administered orally twice a day
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Olaparib | Experimental | This is an open-label, single-arm pilot study of pembrolizumab (study drug) in combination with Olaparib in 20 subjects with advanced BRCA mutation or HDR-defect associated breast cancer having progressed through at least a standard first line therapy. Receives: Drug: Pembrolizumab; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) Per RECIST1.1
Defined as complete or partial response per RECIST 1.1 criteria with assessment every 9 weeks during the first year and while on the study drug, and every 12 weeks thereafter. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions;; Overall Response (OR) = CR + PR
Measured: Up to 2 Years
Secondary outcomes (4)
Progression Free Survival (PFS), Per RECIST 1.1
As measured by RECIST 1.1, in patients progressing after 1st line therapy
Measured: Up to 2 years
Overall Survival (OS)
Calculated in days from the start of treatment to the date of death from any cause
Measured: Up to 2 years
Clinical Benefit Rate (CBR = CR+PR+SD) Per RECIST 1.1
As measured by RECIST 1.1, in patients progressing after 1st line therapy
Measured: Up to 2 years
Duration of Response (DOR) for Complete Response (CR) and Partial Response (PR) Per RECIST 1.1
As measured by RECIST 1.1, in patients progressing after 1st line therapy
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2017 (estimated)
- Study start10 Sep 2017
- Primary completion8 Oct 2024
- Study completion21 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies 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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yuan Yuan
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Yuan Yuan, Cedars-Sinai Medical Center
- Investigators
- Yuan Yuan, MD, Principal investigator, Cedars-Sinal Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03025035
- Sponsor's protocol ID
- IIT2015-18-Mita-MK3475
- Status last verified
- Aug 2026
- First submitted
- 17 Jan 2017
- Last updated
- 28 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label, Phase II Pilot Study of Immune Checkpoint Inhibition With Pembrolizumab in Combination With PARP Inhibition With Olaparib in Advanced BRCA-mutated or HDR-defect Breast Cancers
- ClinicalTrials.gov ID
- NCT03025035
- Acronym / sponsor ID
- IIT2015-18-Mita-MK3475
- Conditions
- Breast Cancer
- Keywords
- BRCA-mutation, Immune checkpoint inhibition, Immunotherapy, Advanced BRCA-mutated breast cancer, HDR-defect, PARP inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Yuan YuanUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 10 Sep 2017 (actual)
- Primary completion
- 8 Oct 2024 (actual)
- Study completion
- 21 Nov 2025 (actual)
- First posted
- 19 Jan 2017 (estimated)
- Results
- Posted 29 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will evaluate the use of immunotherapy and PARP inhibition in a population with incurable advanced breast cancer associated with a germline BRCA mutation or HDR-defect. The main objective is to examine overall response rate of pembrolizumab (immunotherapy) in combination with Olaparib (PARP inhibitor) in advanced BRCA-mutated or Homology-directed repair (HDR)-defect breast cancer.
Detailed description
There are two BRCA genes, BRCA1 and BRCA2, and they play a role in protecting cells from cancer. HDR-defect is another type of gene mutation that can contribute to development and progression of cancer. If one of these genes is mutated, cells may rapidly change and divide, which can lead to cancer. Pembrolizumab is a drug that works with the immune system to target the tumor (immunotherapy). The investigators want to know if combining pembrolizumab and Olaparib therapy will be able to reduce the size and amount of cancer cells with fewer side effects than standard treatment by targeting the tumor. This research study is designed to test the investigational use of pembrolizumab and Olaparib in breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Olaparib | Experimental | Drug: Pembrolizumab, Drug: OlaparibThis is an open-label, single-arm pilot study of pembrolizumab (study drug) in combination with Olaparib in 20 subjects with advanced BRCA mutation or HDR-defect associated breast cancer having progressed through at least a standard first line therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Be willing and able to provide written informed consent/assent for the trial
- Be ≥18 years of age on day of signing informed consent
- Advanced BRCA-mutated and/or HDR-defect breast cancer progressing on or after prior therapy for metastatic disease or locally advanced disease; Prior therapy is defined as follows: for triple negative breast cancer - progressing after at least 1 line of any prior chemotherapy; for HER2 positive disease must have progressed after at least two HER2 directed therapies in the metastatic setting including ado-trastuzumab emtansine (T-DM1); for hormone receptor positive disease (ER, PR, or both) must have progressed after a CDK4/CDK6 inhibitor plus hormonal therapy. Patients with progression within 12 months from previous neoadjuvant or adjuvant treatment could be enrolled in the study as 1st line therapy in metastatic setting.
- Measurable disease by RECIST 1.1, with at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements. Patients with non-measurable bone metastases in addition to measurable disease are eligible; however patients with non-measurable bone disease as the only site(s) of disease are not eligible.
- ECOG 0 or 1
Key exclusion criteria (33 listed)
- Is currently participating or has participated in a study of investigational agent or using an investigational device with 30 days of the first dose of pembrolizumab.
- Is receiving systemic steroid therapy within three days prior to the first dose of pembrolizumab or receiving any other form of immunosuppressive medication
- Is expected to require any other form of systemic or localized antineoplastic therapy while on trial.
- Has participated in another MK03475 trial.
- Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
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-3475Pembrolizumab IV solution administered on Day 1 of each 3-week cycle | Drug | Pembrolizumab + Olaparib |
| OlaparibAlso: LynparzaOlaparib administered orally twice a day | Drug | Pembrolizumab + Olaparib |
Primary outcome
Overall Response Rate (ORR) Per RECIST1.1
Time frame: Up to 2 Years
Defined as complete or partial response per RECIST 1.1 criteria with assessment every 9 weeks during the first year and while on the study drug, and every 12 weeks thereafter. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions;; Overall Response (OR) = CR + PR
4 secondary outcomes
Progression Free Survival (PFS), Per RECIST 1.1
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
Clinical Benefit Rate (CBR = CR+PR+SD) Per RECIST 1.1
Time frame: Up to 2 years
Duration of Response (DOR) for Complete Response (CR) and Partial Response (PR) Per RECIST 1.1
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Yuan Yuan, MD principal investigator
Cedars-Sinal Medical Center
1 site 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 and Olaparib in people with Breast Cancer, run by Yuan Yuan at 1 site in United States.
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 16 inclusion and 33 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: finished, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 29 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) Per RECIST1.1 (time frame: Up to 2 Years). 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 28 Oct 2026.