Actively Recruiting

Phase 2
Age: 18Years +
FEMALE
ID04683679

Phase II Study of Pembrolizumab and Ablative Radiotherapy With or Without Olaparib in Metastatic Triple-Negative or Hormone-Receptor Positive/Her2 Negative Breast Cancers

Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-02-17

34

Participants Needed

7

Research Sites

N/A

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating whether adding pembrolizumab, with or without olaparib, to standard radiation therapy is a safe and effective treatment for women with metastatic triple-negative breast cancer or hormone-receptor positive/Her2 negative breast cancer. The study aims to compare these treatments to radiation therapy alone to see if they provide better outcomes. This is a phase II trial led by Memorial Sloan Kettering Cancer Center focusing on immune therapy combinations to enhance immune responses against these breast cancers. Participants will receive one of several treatment combinations based on their breast cancer subtype. Those with triple-negative breast cancer may receive pembrolizumab with radiation and olaparib, or pembrolizumab with radiation only. Participants with metastatic ER-positive breast cancer will receive pembrolizumab, stereotactic body radiation therapy (SBRT), and olaparib. Pembrolizumab is given as a 30-minute IV infusion every three weeks for three doses. Olaparib is taken orally twice daily without breaks in 21-day cycles for a total of two cycles. Radiation is delivered in 8-9 Gy doses over three fractions, with some accommodations for larger tumors. During the study, participants will undergo regular assessments including radiographic measurements of tumors to evaluate treatment response at eight weeks from baseline. Researchers will monitor overall response rates, organ function through laboratory tests, and side effects. Participants must provide tumor tissue samples for testing. Safety and treatment effects will be closely observed, and follow-up continues as per protocol. The study includes women aged 18 and older with specific breast cancer subtypes and performance status criteria, ensuring careful monitoring throughout participation.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 18Years +
FEMALE

Eligibility Criteria

Eligible

You may qualify if you...

  • Female participants aged 18 years or older
  • Histologically confirmed triple negative breast cancer or ER+/Her2 negative breast cancer
  • Metastatic or recurrent disease for TNBC or ER+ breast cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 30 days prior to enrollment
  • Measurable disease with at least one non-bone metastatic lesion suitable for repeated measurements
  • No more than 3 prior lines of systemic therapy for metastatic TNBC; any number allowed for metastatic ER+ breast cancer
  • At least one tumor site appropriate for palliative radiation therapy
  • Provided archival tumor tissue sample or newly obtained biopsy
  • Not pregnant or breastfeeding, and if a woman of childbearing potential, agrees to use contraceptive guidance during treatment and for one month after last dose
  • Adequate organ function as defined by laboratory values
  • Ability to swallow and retain oral medications
  • Stable corticosteroid dose for at least 4 weeks if receiving corticosteroids
Not Eligible

You will not qualify if you...

  • More than 3 prior lines of systemic therapy in metastatic TNBC patients
  • Positive pregnancy test within 72 hours (urine) or 14 days (serum) prior to treatment
  • Recent anti-cancer therapy or investigational agents within 2 to 4 weeks prior to study treatment
  • Prior radiotherapy within 2 weeks of study treatment start
  • Grade 3 or higher immune-mediated adverse events from prior immunotherapy
  • Live vaccine within 30 days prior to study drug
  • Current participation or recent participation in other investigational studies within 2 to 4 weeks
  • Immunodeficiency or high-dose immunosuppressive therapy within 7 days prior to study drug
  • Active infections requiring systemic therapy
  • Known HIV, active Hepatitis B or C, or active tuberculosis
  • Active autoimmune disease requiring systemic treatment within past 2 years
  • History of severe hypersensitivity to pembrolizumab or olaparib
  • History or current pneumonitis requiring steroids
  • Known additional malignancy requiring treatment within past 2 years (except certain skin or in situ cancers)
  • Major surgery within 2 weeks prior to study treatment
  • Previous allogenic bone marrow or organ transplant
  • Uncontrolled cardiac conditions or serious medical disorders
  • Inability to swallow oral medication or gastrointestinal disorders affecting absorption
  • Use of strong or moderate CYP3A inhibitors or inducers without required washout
  • Psychiatric or substance abuse disorders interfering with trial cooperation
  • Pregnant, breastfeeding, or expecting to conceive during study and 120 days after last treatment
  • Prior enrollment in this study

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

Treatment

Duration - Up to 6 weeks

Participants receive pembrolizumab as an IV infusion every 3 weeks for 3 doses, radiation therapy over 3 fractions, and, depending on the arm, may also take olaparib tablets twice daily continuously for 2 cycles of 3 weeks each.

3 pembrolizumab infusions and radiation over 3 sessions; olaparib taken continuously for 2 cycles (if assigned)

Trial Site Locations

Total: 7 locations

1

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, United States, 07920

Actively Recruiting

2

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, United States, 07748

Actively Recruiting

3

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, United States, 07645

Actively Recruiting

4

Memorial Sloan Kettering Commack (Limited Protocol Activities)

Commack, New York, United States, 11725

Actively Recruiting

5

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, United States, 10604

Actively Recruiting

6

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, United States, 10065

Actively Recruiting

7

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, United States, 11553

Actively Recruiting

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Research Team

A

Atif Khan, MD

S

Simon Powell, MD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

3

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