A Study of Pembrolizumab and Olaparib in People With Endometrial Cancer or Endometrial Carcinosarcoma

NCT05156268 | Completed Phase 2 FDA Drug

• 1 other identifier: 21-447
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to find out whether the combination of pembrolizumab and olaparib is an effective treatment for people with persistent or recurrent endometrial cancer or endometrial carcinosarcoma. The researchers will also look at the safety of the drug combination and whether it causes few or mild side effects in participants.

Conditions

Endometrial Carcinosarcoma

Keywords

Pembrolizumab; Olaparib; Endometrial Carcinosarcoma Recurrent; Endometrial Carcinosarcoma Persistent; 21-447

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  per RECIST 1.1.

  24 weeks

Secondary Outcomes (1)

• Frequency of AE's during therapy

  2 years

Study Arms (1)

Pembrolizumab with Olaparib

EXPERIMENTAL

Eligible patients will receive olaparib in combination with pembrolizumab. Olaparib will be administered orally at 300 mg every 12 hours. Pembrolizumab will be administered intravenously (IV) at 200mg every 3 weeks.

Drug: Pembrolizumab; Drug: Olaparib

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered intravenously (IV) at 200mg every 3 weeks.

Pembrolizumab with Olaparib

Olaparib DRUG

Olaparib will be administered orally at 300 mg every 12 hours.

Pembrolizumab with Olaparib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Endometrial Carcinosarcomas
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed persistent/recurrent endometrial carcinomas. Patients with the following types of endometrial cancer are eligible:
• Serous endometrial cancer (p53 IHC must be confirmed to be aberrant, aberrant p53 expression is consistent with mutant TP53)
• Carcinosarcoma of the endometrium NOTE: For this study, a histological diagnosis of carcinosarcoma must include identifying high grade malignant epithelial and mesenchymal components. The epithelial element must include serous, grade 3 endometrioid, and/or undifferentiated carcinoma (p53 IHC must be confirmed to be aberrant in the high-grade epithelial component, aberrant p53 expression is consistent with mutant TP53). If the epithelial component is grade 3 endometrioid and/or undifferentiated carcinoma, MMR IHC must show retained expression. Patients with known MSI-H tumors are not eligible. Patients with tumors that have known POLE hotspot mutations are not eligible. The mesenchymal component can be homologous or heterologous.
• Grade 3 Endometrioid and/or undifferentiated carcinoma (p53 IHC must be confirmed to be aberrant, aberrant p53 expression is consistent with mutant TP53; MMR IHC must show retained expression. Patients with known MSI-H tumors are not eligible. Patients with tumors that have known POLE hotspot mutations are not eligible).
• Patients must have had at least one but no more than three prior regimens for management of endometrial carcinoma (including neoadjuvant/adjuvant chemotherapy).
• Patients must have had at least one but no more than three prior regimens for management of endometrial carcinoma (including neoadjuvant/adjuvant chemotherapy).
• Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen.
• All chemotherapy must have been completed at least 3 weeks prior to the start of study therapy.
• Hormonal Therapy will NOT count as prior treatment line.
• All hormonal therapy for treatment of endometrial cancer must be discontinued at least one week prior to start of study therapy.
• Have measurable disease based on RECIST 1.1.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have adequate laboratory values as defined in the following table:
• °Hematologic
• Absolute neutrophil count (ANC) ≥1500/μL

You may not qualify if:

• Has received prior therapy with an anti-PD-, anti-PD-L1 or anti-CTLA-4 agent.
• Has received prior PARP inhibitor to include but not limited to olaparib, rucaparib, niraparib, talozaporib.
• Has received prior lenvatinib or other VEGF TKI therapy to include but not limited to lucitinib, cederinib and cabozantonib in combination with anti-PD-1 or anti-PD-L1 therapy.
• Has participated in a study of an investigational agent and received cancer directed study therapy within 4 weeks prior to start of study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drugs. 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 drugs.
• Steroids as CT scan contrast premedication is allowed
• The use of inhaled or topical corticosteroids is allowed
• The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression, and they have been off steroids for at least 4 weeks prior to start of study treatment and remain clinically stable.
• Has severe hypersensitivity to pembrolizumab and/or olaparib.
• 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.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), interstitial lung disease or active, noninfectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

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

Study Sites (6)

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk-Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

pembrolizumab; olaparib

Study Officials

• Maria Rubinstein, 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 is a prospective, single arm, open-label, single-institution phase II trial.

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: December 14, 2021
• Study Start: January 27, 2022
• Primary Completion: April 24, 2026
• Study Completion: April 24, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (6)