A Study of Radiation Therapy With Pembrolizumab and Olaparib or Other Radiosensitizers in Women Who Have Triple-Negative or Hormone-Receptor Positive/Her2 Negative Breast Cancer

NCT04683679 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-505
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to find out whether adding pembrolizumab, with or without olaparib, to standard radiation therapy is a safe and effective treatment for metastatic breast cancer, , and to see whether the study treatment is better than, the same as, or worse than the usual approach (radiation therapy alone).

Conditions

Triple Negative Breast Cancer; TNBC - Triple-Negative Breast Cancer; Breast Cancer; Metastatic Breast Cancer

Keywords

triple-negative breast cancer; TNBC; Breast Cancer; PDL-1 negative; pembrolizumab; olaparib; 20-505; Memorial Sloan Kettering Cancer Center; Metastatic Breast Cancer; Her2

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  To assess overall response rate (ORR) to pembrolizumab + , SBRT + /-olaparib, in non-targeted unirradiated lesions at 8 weeks using RECIST v1.1 in patients with mTNBC who have progressed on ICI or are PD-L1 negative and mER+BC.

  8 weeks from baseline

Study Arms (3)

Arm A

EXPERIMENTAL

Participants will have triple negative breast cancer diagnosis Treatment will be pembro + RT + olaparib

Drug: Pembrolizumab; Drug: Olaparib; Radiation: Radiation

Arm B (the study is amended to pause Arm B)

EXPERIMENTAL

Participants will have triple negative breast cancer diagnosis Treatment will be pembro + RT only

Drug: Pembrolizumab; Radiation: Radiation

Arm C (activate new arm)

EXPERIMENTAL

Participants will have metastatic ER+ breast cancer (ER+ MBC) Treatment will be pembro/SBRT/Olaparib)

Drug: Pembrolizumab; Drug: Olaparib; Radiation: Radiation

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks for 3 doses

Also known as: pembro

Arm A; Arm B (the study is amended to pause Arm B); Arm C (activate new arm)

Olaparib DRUG

Olaparib will be administered twice daily continuously without breaks on a 21-day (3 week) cycle length, for a total of 2 cycles. Olaparib tablets will be administered bid (2 x 150 mg tablets twice daily; total 600 mg daily) on continuous days without interruption for 2 cycles. Each 3 week period constitutes one cycle.

Arm A; Arm C (activate new arm)

Radiation RADIATION

The dose of radiation will be 8-9 Gy x 3 fractions. Radiation therapy will begin on C1D2-7. For tumors that are too large for this schedule, an accomodation of 30 Gy in 6 Gy per fraction is allowed, a schedule commonly used at MSK.

Arm A; Arm B (the study is amended to pause Arm B); Arm C (activate new arm)

Eligibility Criteria

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

You may qualify if:

• Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of triple negative breast cancer or ER+/Her2 will be enrolled in this study.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 30 days prior to the date of allocation/randomization
• Histologically or cytologically-confirmed TNBC (defined as ER \<5%, PR \<5%, HER- 2-neu 0-1+ by IHC or FISH-negative or per MD discretion).
• Histologically of cytologically-confirmed ER+ breast cancer, defined as ER 1-100% and HER-2/neu 0-1+ by IHC or FISH-negative
• Metastatic or recurrent TNBC.
• Metastatic or recurrent ER+ breast cancer
• For mTNBC patients, prior receipt of ICI with progression and/or PDL1-negative. PDL-1 status is not used to determine eligibility among mER+BC patients
• Note: PDL1-status may be determined on tissues from either primary or mTNBC. Determination of PD-L1 status by any prototype assays is acceptable. PD-L1 status is required or archival tissue must be readily available for testing during screening if status was not previously determined.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1. There should be at least one radiographically-confirmed non-bone metastatic lesion that will not undergo RT and is measurable based on RECIST and suitable for repeated measurements.
• Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• No more than 3 prior lines of systemic therapy (including conventional cytotoxics, targeted therapies, biologics, or other invesigational systemic treatments) for inoperable/recurrent or metastatic disease in the TNBC cohort. A line of treatment in this instance refers to any systemic therapy directed at metastatic TNBC and which was discontinued due to disease progression. Treatment discontinued due to toxicity will not be counted. Systemic therapy previously delivered for hormone-receptor positive or Her2+ breast cancer (that has now switched to TNBC subtype) will not count as a prior line of treatment. Any number of prior lines of treatment for mER+BC are allowed.
• At least one tumor site for which palliative RT is considered clinically appropriate. The site under consideration can be a metastatic site, or uncontrolled primary/locally recurrent disease in the breast/chest wall or in the nodes. Prior radiotherapy to the target site is allowed. Investigators should remain within departmental radiotherapy for normal tissue; exceptions should be discussed with the PI.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Formalin- fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Newly-obtained is defined as a specimen obtained up to 30 days prior to initiation of treatment on Day 1 of pembro. (Note: PI can waive this requirement at his discretion if specimen collection is deemed unfeasible).
• A female participant is eligible to participate if she is not pregnant (see Appendix C), not breastfeeding, and at least one of the following conditions applies:

You may not qualify if:

• Receipt of \> 3 lines of systemic therapy in mTNBC patients
• A WOCBP who has a positive urine pregnancy test within 72 hours or a serum pregnancy test within 14 days prior to treatment (see Appendix C). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• A minimum 2-week washout required for all anti-cancer agents, including cytotoxic chemotherapeutic agents, immunotherapy, biologic therapy, and targeted therapies. A 3-4 week washout is preferred when reasonable.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (preferred) or a minimum of 2 weeks prior to the start of study treatment.
• 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. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
• Has previously experienced grade 3 or higher immune-mediated adverse events from prior courses of immunotherapy.
• 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.
• ° Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 (preferred, or 2 weeks minimum) weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been at least 2 weeks (prefer 4 weeks) after the last dose of the previous investigational agent.
• 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 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

pembrolizumab; olaparib; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Atif Khan, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Atif Khan, MD

CONTACT

848-225-6334; khana7@mskcc.org

Simon Powell, MD

CONTACT

212-639-3639

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: December 24, 2020
• Study Start: April 21, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (7)