Olaparib + Pembrolizumab for Breast Cancer

Recruiting at 123 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Chemotherapy, Pembrolizumab

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active infection, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

462 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy of olaparib (MK-7339) plus pembrolizumab (MK-3475) with chemotherapy plus pembrolizumab after induction with first-line chemotherapy plus pembrolizumab in triple negative breast cancer (TNBC). The primary hypotheses are: 1. Olaparib plus pembrolizumab is superior to chemotherapy plus pembrolizumab with respect to progression-free survival (PFS). 2. Olaparib plus pembrolizumab is superior to chemotherapy plus pembrolizumab with respect to overall survival (OS). As of Amendment 3, study enrollment was discontinued. Participants who were receiving benefit from the study intervention could continue treatment until criteria for discontinuation are met. Participants who are on study treatment or in follow-up phase will no longer have tumor response assessments by BICR.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking certain medications that interact with the study drugs, like strong or moderate inhibitors or inducers of CYP3A4, unless they can be stopped before the study.

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

Research shows that Olaparib, a part of this drug combination, significantly improves progression-free survival in patients with certain types of breast cancer, particularly those with BRCA mutations. It has been effective in extending the time patients live without their cancer getting worse compared to standard chemotherapy. ^{1 2 3 4 5}

Is the combination of Olaparib and Pembrolizumab safe for humans?

Olaparib has been studied in combination with carboplatin and has been found to be safe for patients with certain types of breast and ovarian cancer. It has shown clinical benefits and tolerability in breast cancer patients, suggesting it is generally safe for human use. ^{3 5 6 7 8}

How is the drug combination of Olaparib and Pembrolizumab unique for breast cancer treatment?

The combination of Olaparib and Pembrolizumab is unique because it combines a PARP inhibitor (Olaparib) that targets cancer cells with BRCA mutations and an immune checkpoint inhibitor (Pembrolizumab) that helps the immune system attack cancer cells, offering a novel approach for treating certain types of breast cancer. ^{1 5 7 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with triple negative breast cancer (TNBC) that's either inoperable and not previously treated with chemotherapy, or metastatic without prior chemo. Participants should have a life expectancy of at least 27 weeks, be in good physical condition (ECOG status of 0 or 1), have adequate organ function, and agree to use contraception. Pregnant or breastfeeding women, those with certain other cancers or conditions like active CNS metastases, autoimmune diseases requiring recent treatment, severe infections including HIV/Hepatitis B/C, heart failure within the past six months, uncontrolled illnesses that could affect study participation are excluded.

Inclusion Criteria

I have a recent biopsy (within 3 years) of a tumor that wasn't treated with radiation.

I am not pregnant or breastfeeding, can test negative for pregnancy, and will use birth control or abstain from sex.

I agree to use contraception or remain abstinent and not donate sperm while on the study drugs and for 95 days after.

Exclusion Criteria

I am currently being treated for an infection.

I have had serious heart failure or a heart attack in the last 6 months.

I haven't had major surgery in the last 2 weeks or still recovering from one.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive first-line chemotherapy plus pembrolizumab

6-12 weeks

Every 3 weeks

Post-Induction Treatment

Participants receive either olaparib plus pembrolizumab or chemotherapy plus pembrolizumab

21-day cycles, up to 29 months

Day 1 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 29 months

Treatment Details

Interventions

• Carboplatin
• Gemcitabine
• Olaparib
• Pembrolizumab

Trial Overview The study compares two treatments after initial chemo plus pembrolizumab: one group will receive olaparib plus pembrolizumab while the other continues on standard chemotherapy plus pembrolizumab. The goal is to see which combination is better at stopping cancer progression (PFS) and improving survival rates (OS). Enrollment has stopped but ongoing participants can continue if benefiting.

Participant Groups

Group I: Pembrolizumab + Olaparib Experimental Treatment 2 Interventions

This arm includes participants who randomized following completion of the induction period. After the induction period, participants received pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle plus olaparib 300 mg orally twice daily during the post-induction period.

Group II: Pembrolizumab + Carboplatin + Gemcitabine Experimental Treatment 3 Interventions

This arm includes participants who randomized following completion of the induction period. Participants continued to receive both carboplatin AUC 2 with gemcitabine 1000 mg/m\^2 intravenously on Days 1 and 8 of each 21-day cycle in addition to pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle in the post-induction period.

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

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

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

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

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

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

Olaparib, a PARP inhibitor, has shown significant clinical benefits in improving progression-free survival for patients with BRCA1 or BRCA2 mutated HER2 negative metastatic breast cancer compared to standard chemotherapy.

The drug has a manageable safety profile, making it a promising treatment option, particularly for triple negative breast cancer, although further research is needed to optimize its use with other therapies and identify suitable biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. Griguolo, G., Dieci, MV., Guarneri, V., et al.[2019]

In the phase III OlympiAD trial, olaparib significantly improved progression-free survival (PFS) in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer, with a median PFS of 8.0 months compared to 3.8 months for chemotherapy, indicating a strong efficacy of olaparib.

Subgroup analyses showed consistent benefits of olaparib across various patient characteristics, including hormone receptor status and prior chemotherapy, with higher objective response rates and improved quality of life compared to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib efficacy in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer: Subgroup analyses from the phase III OlympiAD trial. Senkus, E., Delaloge, S., Domchek, SM., et al.[2023]

The combination of olaparib and carboplatin was found to be safe and effective in treating breast and ovarian cancer in patients with germline BRCA1 or BRCA2 mutations, with 50% of patients showing a partial response and one patient achieving a complete response.

Proteomic analysis indicated that high levels of FOXO3a expression before treatment may predict a better response to the therapy, suggesting a potential biomarker for future studies.

NCBI (Pubmed)

pubmed.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. Lee, JM., Hays, JL., Annunziata, CM., et al.[2022]

In the phase IIIb LUCY trial, olaparib demonstrated a median progression-free survival (PFS) of 8.11 months in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer, indicating its effectiveness in this patient population.

The treatment was generally well-tolerated, with 48.6% of patients showing a clinical response; however, 25.4% experienced grade 3 or higher treatment-emergent adverse events, including significant cases of anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis. Gelmon, KA., Fasching, PA., Couch, FJ., et al.[2021]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

A phase II study of the PARP inhibitor olaparib confirmed its clinical benefits for cancer patients with inherited BRCA1 and BRCA2 mutations, particularly in advanced breast and ovarian cancers.

The study also provided evidence that olaparib is effective against pancreatic and prostate cancers, expanding its potential use in treating various cancer types associated with these genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib shows promise in multiple tumor types. [2014]

Olaparib, an oral PARP-inhibitor, significantly improves progression-free survival in HER2-negative advanced breast cancer patients with BRCA1/2 mutations compared to standard chemotherapy, based on a randomized Phase III trial.

The trial also indicated an overall survival benefit for patients who had not received prior chemotherapy for metastatic disease, highlighting olaparib's potential as an effective treatment option in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. Griguolo, G., Dieci, MV., Miglietta, F., et al.[2021]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Olaparib efficacy in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer: Subgroup analyses from the phase III OlympiAD trial. [2023]

3. United States pubmed.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]

4. England pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Olaparib shows promise in multiple tumor types. [2014]

7. England pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]