Pembrolizumab + Olaparib for Breast Cancer

Overseen By Amy Oppenheim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yuan Yuan

Must not be taking: Steroids, Immunosuppressants, CYP3A inhibitors, CYP3A inducers

Disqualifiers: Active CNS metastases, Autoimmune disease, HIV, Hepatitis, 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: 9

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, pembrolizumab (an immunotherapy drug) and olaparib (a PARP inhibitor), to evaluate their effectiveness in treating advanced breast cancer. The focus is on patients whose cancer is linked to specific genetic issues, such as BRCA mutations or HDR defects, and who have not responded to previous treatments. It suits those who have progressed after standard therapies and have breast cancer associated with these genetic factors. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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

The trial requires a washout period (time without taking certain medications) for specific drugs. If you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them for 2 to 5 weeks before starting the trial. Additionally, if you are on systemic steroid therapy or certain antineoplastic therapies, you may need to discontinue them before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of pembrolizumab and olaparib has been tested in patients with certain advanced tumors. These studies found the combination to be generally safe, with no new safety issues reported. Patients tolerated the combination well, experiencing no unexpected side effects. Previous patients with similar gene mutations also demonstrated a tolerable safety profile. These findings suggest that the treatment could be a safe option for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab and olaparib for advanced breast cancer because it offers a novel approach by targeting both the immune system and DNA repair mechanisms. Pembrolizumab works by unleashing the immune system to attack cancer cells, while olaparib is a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to cell death. This dual mechanism is different from the standard treatments, which often rely on chemotherapy or hormone therapy alone, and it holds promise for more effective outcomes, especially in patients with BRCA mutations or HDR-defect associated breast cancer.

What evidence suggests that pembrolizumab and olaparib might be an effective treatment for advanced breast cancer?

Research shows that combining pembrolizumab and olaparib may help treat advanced breast cancer in individuals with specific genetic traits, such as BRCA mutations or HDR defects. This trial will evaluate the combination in participants with these genetic features. Studies have found that this treatment can shrink tumors in some patients with these profiles. Pembrolizumab aids the immune system in fighting cancer cells, while olaparib inhibits a protein necessary for cancer cell repair. Early results suggest this combination is effective against tumors, with no new safety concerns identified, indicating potential effectiveness for those with the targeted genetic profiles. ^{1 3 4 6 7}

Who Is on the Research Team?

Yuan Yuan, MD PhD

Principal Investigator

Cedars-Sinal Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced breast cancer that's linked to a BRCA mutation or HDR-defect. Participants must have measurable disease, adequate organ function, and a life expectancy of at least 16 weeks. Women should be postmenopausal or use two forms of contraception; men must use condoms. Exclusions include recent other treatments, additional cancers needing treatment, inability to take oral meds, certain infections like HIV/Hepatitis B/C, active autoimmune diseases, and known allergies to the drugs tested.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My organs are functioning well.

You are expected to live for at least 16 more weeks.

Exclusion Criteria

I am not on steroids or immunosuppressants as of three days ago.

I have a history of HIV or active Hepatitis B/C.

I have an autoimmune disease treated with medication in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab in combination with Olaparib for advanced BRCA-mutated or HDR-defect breast cancer

Up to 2 years

Assessments every 9 weeks during the first year and every 12 weeks thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Pembrolizumab

Trial Overview The study tests pembrolizumab (an immunotherapy drug) combined with olaparib (a PARP inhibitor) in patients with incurable advanced breast cancer due to BRCA mutations or HDR defects. The main goal is to see how well this combination works by measuring the overall response rate according to specific criteria.

How Is the Trial Designed?

Group I: Pembrolizumab + Olaparib Experimental Treatment 2 Interventions

This is an open-label, single-arm pilot study of pembrolizumab (study drug) in combination with Olaparib in 20 subjects with advanced BRCA mutation or HDR-defect associated breast cancer having progressed through at least a standard first line therapy.

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?

Yuan Yuan

Lead Sponsor

Trials

2

Recruited

30+

Monica Mita

Lead Sponsor

Trials

3

Recruited

100+

Merck Sharp & Dohme LLC

Industry 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

Citations

1. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P3-10-19/754020/Abstract-P3-10-19-Phase-II-Trial-of-Pembrolizumab

Phase II Trial of Pembrolizumab in Combination with Olaparib ... This study was designed to test the effectiveness of this combination in breast cancer patients with HRD defects or BRCA mutations. Methods: ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03025035

Study Details | NCT03025035 | Pembrolizumab in ... The main objective is to examine overall response rate of pembrolizumab (immunotherapy) in combination with Olaparib (PARP inhibitor) in advanced BRCA-mutated ...

3. mdanderson.org mdanderson.org/newsroom/aacr-olaparib-and-pembrolizumab-combination-shows-early-promise-in-molecularly-selected-tumor-agnostic-trial.h00-159775656.html

AACR: Olaparib and pembrolizumab combination shows ... The combination of the PARP inhibitor olaparib and the PD-1 inhibitor pembrolizumab showed initial antitumor activity with no new safety signals.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12238646/

A phase II single-arm study of combination pembrolizumab ... All BTC patients do not appear to benefit from pembrolizumab plus olaparib, but those with HRR deficiencies and/or IDH mutations may benefit ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03025035/pembrolizumab-in-combination-with-olaparib-in-advanced-brca-mutated-or-hdr-defect-breast-cancer

Pembrolizumab in Combination With Olaparib in Advanced ... The main objective is to examine overall response rate of pembrolizumab (immunotherapy) in combination with Olaparib (PARP inhibitor) in ...

6. onclive.com onclive.com/view/olaparib-plus-pembrolizumab-shows-efficacy-in-hrr-gene-mutated-advanced-tumors-with-without-hrd-positivity

Olaparib Plus Pembrolizumab Shows Efficacy in HRR ... Olaparib plus pembrolizumab was safe and effective in HRR gene–mutated and/or HRD-positive advanced tumors.

7. merck.com merck.com/news/new-and-updated-data-for-mercks-keytruda-pembrolizumab-and-updated-data-on-lynparza-olaparib-in-multiple-breast-cancer-subtypes-to-be-presented-at-the-2017-san-antonio-breast/

New and Updated Data for Merck's KEYTRUDA® ... New and Updated Data for Merck's KEYTRUDA® (pembrolizumab) and Updated Data on LYNPARZA® (olaparib) in Multiple Breast Cancer Subtypes to Be Presented at the ...