Olaparib + Pembrolizumab for Breast Cancer

Recruiting at 7 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

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will test any good and bad effects of combining the study drugs pembrolizumab and olaparib, given before the standard surgical procedure, to treat TNBC or HR+ HER2- breast cancers. The study drugs could shrink cancer, but they could also cause side effects. The study researchers want to find out whether the study drugs will shrink the cancer by a certain percentage compared with its current size, which may improve the outcome of surgery.

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.

What data supports the idea that Olaparib + Pembrolizumab for Breast Cancer is an effective treatment?

The available research shows that Olaparib, when used alone, has been effective in treating breast cancer, especially in patients with specific genetic mutations (BRCA1 or BRCA2). In a study, patients with these mutations who took Olaparib had a longer period without the cancer getting worse compared to those who received standard chemotherapy. For example, in one trial, patients taking Olaparib had about 8 months without cancer progression, while those on standard treatment had about 4 months. This suggests that Olaparib is more effective than some traditional treatments for certain breast cancer patients. However, there is no specific data provided on the combination of Olaparib with Pembrolizumab for breast cancer in the information available. ^{1 2 3 4 5}

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

Research shows that Olaparib helps patients with certain types of breast cancer live longer without the disease getting worse. It is especially effective for those with specific genetic mutations (BRCA1 or BRCA2) and has been shown to work better than standard chemotherapy in these cases. ^{1 2 3 4 5}

What safety data is available for the treatment with Olaparib and Pembrolizumab for breast cancer?

The provided research does not directly address the safety data for the combination of Olaparib (Lynparza) and Pembrolizumab (KEYTRUDA) for breast cancer. However, Olaparib has been studied in various trials for breast and ovarian cancer, showing clinical benefits and tolerability as a single agent and in combination with other treatments. The safety of Olaparib has been evaluated in different contexts, such as in combination with carboplatin, and it has shown promise in multiple tumor types, including breast cancer. Pembrolizumab, known as KEYTRUDA, is not specifically mentioned in the provided research, so additional sources would be needed to find safety data for its combination with Olaparib in breast cancer treatment. ^{1 4 6 7 8}

Is the combination of Olaparib and Pembrolizumab safe for humans?

Olaparib has been studied in various cancers, including breast and ovarian cancer, and is generally considered safe when used alone or with other treatments like carboplatin. However, specific safety data for the combination of Olaparib and Pembrolizumab is not provided in the available research. ^{1 4 6 7 8}

Is the drug Olaparib, Pembrolizumab a promising treatment for breast cancer?

Yes, Olaparib, also known as Lynparza, is a promising drug for breast cancer, especially for patients with specific genetic mutations (BRCA1/2). It has shown benefits in improving survival rates and is effective in treating certain types of breast cancer, like HER2-negative and triple-negative breast cancer. ^{1 2 6 7 9}

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 immunotherapy drug (Pembrolizumab) that helps the immune system attack cancer cells, offering a novel approach for treating certain types of breast cancer. ^{1 2 6 7 9}

Research Team

Ayca Gucalp, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Your tumor should be at least 1.5 cm in size.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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, 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]

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

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

2. England pubmed.ncbi.nlm.nih.gov

Olaparib for the treatment of breast cancer. [2019]

3. 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]

4. 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]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. [2021]

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

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

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

Olaparib shows promise in multiple tumor types. [2014]

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]