Pembrolizumab in Combination With Olaparib in Advanced BRCA-mutated or HDR-defect Breast Cancer

NCT03025035 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IIT2015-18-Mita-MK3475
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Breast Cancer

Keywords

BRCA-mutation; Immune checkpoint inhibition; Immunotherapy; Advanced BRCA-mutated breast cancer; HDR-defect; PARP inhibitor

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) Per RECIST1.1

  Defined as complete or partial response or stable disease 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; Stable Disease (SD), a tumor that is neither shrinking sufficiently to be considered a partial response (PR) (at least 30% decrease in tumor burden), nor growing significantly enough to be considered progressive disease (PD) (more than 20% increase in tumor burden); Overall Response (OR) = CR + PR + SD

  Up to 2 Years

Secondary Outcomes (4)

• Progression Free Survival (PFS), Per RECIST 1.1

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

• Clinical Benefit Rate (CBR = CR+PR+SD) Per RECIST 1.1

  Up to 2 years

• Duration of Response (DOR) for Complete Response (CR) and Partial Response (PR) Per RECIST 1.1

  Up to 2 years

Study Arms (1)

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.

Drug: Pembrolizumab; Drug: Olaparib

Interventions

Pembrolizumab DRUG

Pembrolizumab IV solution administered on Day 1 of each 3-week cycle

Also known as: Keytruda, MK-3475

Pembrolizumab + Olaparib

Olaparib DRUG

Olaparib administered orally twice a day

Also known as: Lynparza

Pembrolizumab + Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.
• a. 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.

Sponsors & Collaborators

• Yuan Yuan: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Yuan Yuan, MD, PhD
• Organization: Cedars-Sinai Medical Center

yuan.yuan@cshs.org

3108888680

Study Officials

• Yuan Yuan, MD

  Cedars-Sinal Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Breast Oncology

Study Record Dates

• First Submitted: January 17, 2017
• First Posted: January 19, 2017
• Study Start: September 10, 2017
• Primary Completion: October 8, 2024
• Study Completion: November 21, 2025
• Last Updated: February 6, 2026
• Results First Posted: May 29, 2025

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)