300 Participants Needed

Olaparib + Pembrolizumab for Advanced Cancer

Recruiting at 145 trial locations
TF
Overseen ByToll Free Number
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Merck Sharp & Dohme Corp.
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 assess the efficacy and safety of treatment with olaparib (MK-7339) in combination with pembrolizumab (MK-3475) in adults with previously treated, advanced (metastatic and/or unresectable) Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-positive solid tumors.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that affect the liver enzyme CYP3A4. If you are on strong or moderate inhibitors or inducers of CYP3A4, you will need to stop them for a specific period before starting the trial: 2 weeks for inhibitors and up to 5 weeks for inducers like phenobarbital.

What data supports the effectiveness of the drug combination Olaparib and Pembrolizumab for advanced cancer?

Research shows that Pembrolizumab and Olaparib, when used together, have shown activity in treating metastatic castration-resistant prostate cancer, a type of advanced cancer. Additionally, Pembrolizumab has been effective in improving survival in patients with advanced non-small-cell lung cancer when used with other treatments.12345

Is the combination of Olaparib and Pembrolizumab safe for humans?

Olaparib (also known as Lynparza) has been tested in various studies for conditions like ovarian and breast cancer, showing it can be used safely in humans. While specific safety data for the combination with Pembrolizumab (KEYTRUDA) isn't provided, Olaparib alone has been administered safely in clinical trials.678910

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

The combination of Olaparib and Pembrolizumab is unique because it combines a PARP inhibitor (Olaparib) that targets cancer cells with DNA repair issues, often seen in BRCA mutations, with an immunotherapy drug (Pembrolizumab) that helps the immune system recognize and attack cancer cells. This dual approach may offer a novel way to treat advanced cancers by addressing both genetic vulnerabilities and enhancing immune response.6791112

Research Team

MD

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

Adults with advanced solid tumors that have specific genetic mutations or deficiencies, who've had some response to platinum-based therapies and are not eligible for curative treatment. They must be in relatively good health, agree to contraception, and not be pregnant or breastfeeding. Exclusions include certain blood disorders, active infections or autoimmune diseases, recent treatments with other cancer drugs or vaccines, and known allergies to trial medications.

Inclusion Criteria

My last cancer treatment, which included platinum-based therapy, was effective.
My cancer has harmful mutations in specific genes related to DNA repair.
My cancer responded to platinum-based treatment without becoming resistant.
See 7 more

Exclusion Criteria

I am not on high-dose steroids or other drugs that weaken my immune system.
I have not received a live vaccine in the last 30 days.
I have received an organ or tissue transplant from another person.
See 24 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib 300 mg via oral tablet 2 times each day plus pembrolizumab 200 mg via intravenous infusion on Day 1 of each 21-day cycle. Treatment may continue for up to approximately 2 years.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

  • Olaparib
  • Pembrolizumab
Trial OverviewThe trial is testing the combination of two drugs: Olaparib (MK-7339), which targets cancer cells with DNA repair issues; and Pembrolizumab (MK-3475), an immunotherapy drug. The study aims to see how well these drugs work together in treating patients whose tumors have specific genetic features making them hard to treat.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Olaparib+PembrolizumabExperimental Treatment2 Interventions
Participants receive olaparib 300 mg via oral tablet 2 times each day PLUS pembrolizumab 200 mg via intravenous infusion on Day 1 of each 21-day cycle. Participants may receive olaparib+pembrolizumab for up to approximately 2 years.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials
2,287
Recruited
4,582,000+
Chirfi Guindo profile image

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis profile image

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead Sponsor

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

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

Robert M. Davis profile image

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 the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.
Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.
Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater.Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]
In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.
Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC.Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]
In a phase III study involving 793 participants with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), the combination of pembrolizumab and olaparib did not significantly improve radiographic progression-free survival (rPFS) or overall survival (OS) compared to next-generation hormonal agents (NHA).
Although the combination therapy showed a higher objective response rate (16.8% vs. 5.9% for NHA), the study was ultimately stopped for futility, indicating that it did not provide a meaningful benefit in prolonging survival or delaying disease progression.
Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial.Antonarakis, ES., Park, SH., Goh, JC., et al.[2023]

References

Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study. [2023]
Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]
Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. [2023]
A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. [2021]
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: an oral PARP-1 and PARP-2 inhibitor with promising activity in ovarian cancer. [2016]
Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]
10.United Statespubmed.ncbi.nlm.nih.gov
Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. [2022]
Olaparib: A Review as First-Line Maintenance Therapy in Advanced Ovarian Cancer. [2022]
Olaparib for the treatment of breast cancer. [2019]