A Study of Olaparib and Pembrolizumab in People With Triple Negative Breast Cancer (TNBC) or Hormone Receptor-positive HER2-negative Breast Cancer

NCT05203445 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 21-018
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 7

Brief Summary

This study will test any good and bad effects of combining the study drugs pembrolizumab and olaparib, given before the standard surgical procedure, to treat TNBC or HR+ HER2- breast cancers. The study drugs could shrink cancer, but they could also cause side effects. The study researchers want to find out whether the study drugs will shrink the cancer by a certain percentage compared with its current size, which may improve the outcome of surgery.

Conditions

Breast Cancer

Keywords

Stage T1c-3N0-3; Olaparib; Pembrolizumab; 21-018

Outcome Measures

Primary Outcomes (1)

• pathologically negative MRI-guided biopsy

  Biopsy-confirmed radiographic complete response will be determined at the 12-week timepoint. pCR/RCB0 will be determined at the time of surgery.

  12 weeks

Study Arms (1)

Olaparib in Combination with Pembrolizumab

EXPERIMENTAL

Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks in conjunction with olaparib (for the first 12 weeks) and cytotoxic chemotherapy (after olaparib has been completed) if administered prior to surgery and if the patient is not deemed to have tumor growth.

Drug: Olaparib; Drug: Pembrolizumab

Interventions

Olaparib DRUG

Olaparib 300 mg orally BID

Olaparib in Combination with Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab 400 mg intravenously q6weeks

Olaparib in Combination with Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Ability to comply with protocol, in the investigator's judgment
• Newly diagnosed histologically confirmed Stage T1c-3N0-3:
• TNBC (ER/PgR negativity will be defined using IHC per ASCO/CAP criteria/HER2-negativity will be defined using ISH or IHC assays per ASCO/CAP criteria) OR
• Hormone receptor-positive, HER2-negative breast cancer defined as per ASCO/CAP criteria
• Measurable disease per RECIST v1.1
• Minimum tumor size of 1.5 cm
• All patients must have a germline mutation in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
• ECOG Performance Status of 0 or 1
• Patient agreement to undergo appropriate surgical management including, if indicated, axillary lymph node surgery and partial or total mastectomy after completion of neoadjuvant treatment. Note: consideration of neoadjuvant treatment will be determined by disease management team based on the subtypes and minimum size the tumor has to be.
• Baseline LVEF ≥ 53% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans
• Have adequate organ function as defined by the following laboratory results obtained within 14 days prior to the first study treatment
• Hematological
• Absolute neutrophil count (ANC) ≥1500/μL
• Platelets ≥100 000/μL

You may not qualify if:

• Prior history of invasive breast cancer
• Stage IV (metastatic) breast cancer
• Prior systemic therapy for treatment and prevention of breast cancer
• Contraindication to MRI scan and/or allergy to intravenous contrast-gadolinium
• 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 (eg, CTLA-4, OX-40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past X 3 years prior to screening. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ are not excluded. Patients with prior ductal/lobular carcinoma in situ are not excluded if they were treated exclusively with mastectomy \> 3 years prior to diagnosis of current breast cancer.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab or olaparib and/or any of its excipients.
• Has 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). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has 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). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Severe infections within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

olaparib; pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Ayca Gucalp, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This trial is designed as a single-arm, open-label, non-randomized study.

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: January 24, 2022
• Study Start: January 31, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (7)