26 Participants Needed

Pembrolizumab + Olaparib for Endometrial Cancer

Recruiting at 6 trial locations
MR
Vicky Makker, MD - MSK Gynecologic ...
Overseen ByVicky Makker, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop any hormonal therapy for endometrial cancer at least one week before starting. If you are taking strong or moderate inhibitors or inducers of CYP3A4, you will need to stop them for a washout period of 2 to 5 weeks before starting the study. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drugs Pembrolizumab and Olaparib for treating endometrial cancer?

Pembrolizumab has shown a meaningful response rate in patients with advanced endometrial cancer that has specific genetic features (MSI-H/dMMR), as seen in the KEYNOTE-158 study. Additionally, a case report showed that a combination of Olaparib and Pembrolizumab, along with another drug, was effective in treating a different type of cancer, suggesting potential benefits of this combination.12345

Is the combination of Pembrolizumab and Olaparib safe for humans?

Olaparib (Lynparza) has been studied for safety in various cancers, including ovarian and breast cancer, and is generally considered safe when used as a single agent or in combination with other treatments. Pembrolizumab (KEYTRUDA) is also widely used and has a known safety profile. However, specific safety data for the combination of Pembrolizumab and Olaparib in endometrial cancer is not provided in the available research.56789

How is the drug combination of Pembrolizumab and Olaparib unique for treating endometrial cancer?

This drug combination is unique because Pembrolizumab, an immunotherapy drug, is used to enhance the body's immune response against cancer cells, while Olaparib, a PARP inhibitor, targets cancer cell DNA repair mechanisms. This combination may offer a novel approach for patients with advanced endometrial cancer, especially those with specific genetic markers like microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), where traditional treatments may not be effective.1231011

Research Team

MR

Maria Rubinstein, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with certain types of endometrial cancer who've had no more than three prior treatments (excluding hormonal therapy). They must have measurable disease, be in good physical condition, and not be pregnant or breastfeeding. People with severe allergies to the drugs being tested, active autoimmune diseases, recent immunosuppressive therapies, or uncontrolled illnesses cannot participate.

Inclusion Criteria

I stopped my hormonal therapy for endometrial cancer at least a week ago.
My endometrial cancer has come back or did not go away after treatment.
My endometrial cancer is either serous, carcinosarcoma, grade 3 endometrioid, or undifferentiated.
See 11 more

Exclusion Criteria

I have a significant liver condition.
I have been diagnosed with MDS, AML, or have symptoms suggesting these conditions.
I have been treated with drugs targeting PD-1, PD-L1, or CTLA-4.
See 14 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib orally at 300 mg every 12 hours and pembrolizumab intravenously at 200 mg every 3 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

  • Olaparib
  • Pembrolizumab
Trial OverviewResearchers are testing a combination of two drugs—Pembrolizumab and Olaparib—to treat persistent or recurrent endometrial cancer. The study aims to determine the effectiveness and safety of this drug duo while monitoring for mild side effects in participants.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Pembrolizumab with OlaparibExperimental Treatment2 Interventions
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.

Olaparib is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as Lynparza for:
  • Breast cancer
  • Ovarian cancer
  • Fallopian tube cancer
  • Peritoneal cancer
  • Pancreatic cancer
  • Prostate cancer
  • Endometrial cancer
🇺🇸
Approved in United States as Lynparza for:
  • Ovarian, fallopian tube, and primary peritoneal cancer
  • Breast cancer
  • Prostate cancer
  • Pancreatic cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials
4,096
Recruited
5,232,000+
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Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

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Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a study of 48 patients with recurrent endometrial cancer treated with pembrolizumab and lenvatinib, the best objective response rate was 23.8%, indicating a lower effectiveness compared to clinical trial results.
The treatment was associated with notable side effects, with 56.2% of patients requiring a dose reduction of lenvatinib and 16.7% discontinuing treatment due to adverse events, highlighting the importance of monitoring for safety in real-world settings.
Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea.Kim, J., Noh, JJ., Lee, TK., et al.[2022]
In a study of 44 women with advanced or recurrent MMRd/MSI-H endometrial adenocarcinomas treated with pembrolizumab, obesity (BMI≥30) was linked to a higher disease control rate (85.2%) compared to those with a BMI<30 (59.8%).
Patients with obesity also experienced significantly longer progression-free survival (PFS) while overall survival (OS) rates remained similar regardless of BMI, suggesting that body weight may influence treatment outcomes with pembrolizumab.
Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab.Bernard, L., How, JA., Patel, S., et al.[2023]
In the KEYNOTE-158 study, pembrolizumab showed a clinically meaningful objective response rate in patients with advanced MSI-H/dMMR endometrial cancer, with 84 out of 90 patients completing health-related quality of life (HRQoL) assessments.
Patients receiving pembrolizumab experienced significant improvements in their quality of life, with mean scores on the QLQ-C30 and EQ-5D-3L questionnaires increasing notably, especially among those who achieved a complete or partial response to treatment.
Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study.O'Malley, DM., Bariani, GM., Cassier, PA., et al.[2022]

References

Real-world experience of pembrolizumab and lenvatinib in recurrent endometrial cancer: A multicenter study in Korea. [2022]
Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. [2023]
Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. [2022]
Remarkable Response to the Triplet Combination of Olaparib with Pembrolizumab and Bevacizumab in the Third-Line Treatment of an Ovarian Clear Cell Carcinoma Patient with an ARID1A Mutation: A Case Report. [2022]
New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]
Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. [2020]
Olaparib: first global approval. [2020]
Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
New Approved Use for Keytruda. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium. [2023]