Olaparib + Pembrolizumab for Breast Cancer

Not currently recruiting at 8 trial locations

Overseen By Ayca Gucalp, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids, Live vaccines, others

Disqualifiers: Metastatic cancer, Autoimmune disease, 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: 6

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a combination of two drugs, pembrolizumab (an immunotherapy drug) and olaparib (a targeted therapy drug), affects breast cancer when administered before surgery. Researchers aim to determine if these drugs can shrink tumors in triple-negative (TNBC) or hormone receptor-positive, HER2-negative breast cancers, potentially improving surgical outcomes. Candidates for the trial include individuals with newly diagnosed breast cancer and specific genetic mutations (BRCA1, BRCA2, PALB2, RAD51C, or RAD51D). As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in breast cancer treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you have received certain treatments like systemic anti-cancer therapy within 4 weeks, radiotherapy within 2 weeks, or live vaccines within 30 days before the trial. It's best to discuss your specific medications with the trial team.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic steroids or immunosuppressive therapy, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that the combination of olaparib and pembrolizumab is likely to be safe for humans?

Research has shown that using olaparib and pembrolizumab together may help treat certain cancers. The side effects of this combination are generally manageable. Common side effects include anemia (low red blood cell count), nausea (feeling sick to the stomach), and fatigue (feeling very tired). Importantly, studies have not identified any new safety concerns so far. This suggests the treatment is fairly well-tolerated, though, like any medical treatment, potential risks exist. Overall, the current evidence offers some reassurance about the safety of this combination therapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Olaparib and Pembrolizumab for breast cancer because it introduces a novel approach compared to existing treatments. Unlike traditional therapies that often rely on chemotherapy alone, Olaparib is a PARP inhibitor that specifically targets cancer cells with DNA repair defects, potentially leading to more effective cancer cell destruction. Pembrolizumab, an immunotherapy drug, helps the immune system recognize and attack cancer cells more efficiently. This dual-action strategy of targeting cancer both on a genetic level and through immune activation makes it a promising advancement over standard treatments.

What evidence suggests that the combination of olaparib and pembrolizumab could be effective for breast cancer?

Research shows that combining the drugs olaparib and pembrolizumab may help treat certain cancers. This trial will administer this combination to evaluate its effectiveness and safety for breast cancer patients with specific genetic traits, such as changes in HRR genes or HRD positivity. In earlier studies, about one-third of breast cancer patients experienced tumor shrinkage with this treatment. The treatment is generally well tolerated and has not revealed any new safety issues. These results suggest potential benefits for patients with TNBC or HR+ HER2- breast cancers. ^{2 3 4 5 6}

Who Is on the Research Team?

Ayca Gucalp, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed Stage T1c-3N0-3 Triple Negative Breast Cancer or Hormone Receptor-positive HER2-negative breast cancer, who have a certain gene mutation (BRCA1/2, PALB2, RAD51C/D). They must be able to undergo surgery after treatment and agree to use contraception. Exclusions include prior cancer treatments within 4 weeks, severe allergies to the drugs being tested, active infections or pneumonitis, certain heart conditions, and pregnancy.

Inclusion Criteria

Your tumor should be at least 1.5 cm in size.

Ability to comply with protocol, in the investigator's judgment

My recent tests show my organs are functioning well.

Exclusion Criteria

I am a woman of childbearing potential and my recent pregnancy test was positive.

I have not taken any strong antibiotics in the last 2 weeks.

My breast cancer has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and olaparib before surgery to treat TNBC or HR+ HER2- breast cancers

12 weeks

Pembrolizumab every 6 weeks, olaparib for the first 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Pembrolizumab

Trial Overview The study tests combining Olaparib and Pembrolizumab before surgery in patients with specific types of breast cancer. The goal is to see if these drugs can shrink tumors more effectively than current standards. Participants will receive both medications and their tumor size will be measured for comparison.

How Is the Trial Designed?

Group I: Olaparib in Combination with Pembrolizumab Experimental Treatment 2 Interventions

Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks in conjunction with olaparib (for the first 12 weeks) and cytotoxic chemotherapy (after olaparib has been completed) if administered prior to surgery and if the patient is not deemed to have tumor growth.

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?

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+

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

Published Research Related to This Trial

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, 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]

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, 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]

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]

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]

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]

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]

Citations

1. 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.

2. 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 ... Conclusions: The combination of olaparib and pembrolizumab was well tolerated, with ORR of 33.3% in heavily pretreated breast cancer patients, ...

3. 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® ... The KEYTRUDA (pembrolizumab) breast cancer clinical development program encompasses 15 internal and external collaborative studies across multiple breast cancer ...

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. 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.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2949820124000390

Real-world safety and effectiveness of neoadjuvant ... Original article. Real-world safety and effectiveness of neoadjuvant chemotherapy combination with pembrolizumab in triple-negative breast cancer.