Olaparib + Pembrolizumab for Breast Cancer
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo Group
Prior Safety Data
Breakthrough Therapy
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.
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.
12345What 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.
14678Is 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.
12679Eligibility 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.
+9 more
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.
+19 more
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Olaparib in Combination with PembrolizumabExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Middletown, NJ
Memorial Sloan Kettering Westchester (Limited Protocol Activities)Harrison, NY
Memorial Sloan Kettering Westchester (Limited Protocol Activities)West Harrison, NY
Memorial Sloan Kettering Nassau (Limited Protocol Activities)Uniondale, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]Olaparib (Lynparza) is now approved for the adjuvant treatment of adult patients who have, or are suspected to have, the germline variation of BRCA-mutated human epidermal growth factor receptor 2-negative high-risk early breast cancer and who were previously treated with neoadjuvant or adjuvant chemotherapy.
Olaparib for the treatment of breast cancer. [2019]Mutations in BRCA1 and BRCA2 genes account for around 2-3% of breast cancer events and more than 10% of triple negative breast cancers. Olaparib (Lynparza®), an orally administered PARP inhibitor, demonstrated clinical benefit in a phase III trial for mutated BRCA-positive HER2 negative metastatic breast cancer. Areas covered: This review gives an overview of available preclinical and clinical data regarding olaparib, including its chemistry, mechanism of action, pharmacokinetics and pharmacodynamics, and evidence supporting antitumor efficacy and safety profile in breast cancer patients. Expert commentary: Olaparib improves progression-free survival in germline BRCA mutated HER2 negative metastatic breast cancer patients as compared to standard chemotherapy, with a manageable toxicity profile. Efficacy is of clinical relevance especially in the context of triple negative breast cancer. However, several aspects, such as sequencing or combination of these agents with other anticancer agents and identification of appropriate biomarkers, still need to be clearly defined.
Olaparib efficacy in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer: Subgroup analyses from the phase III OlympiAD trial. [2023]In the primary analysis of the phase III OlympiAD trial, olaparib significantly prolonged progression-free survival (PFS) vs chemotherapy treatment of physician's choice (TPC) in patients with germline BRCA-mutated (gBRCAm), HER2-negative metastatic breast cancer (mBC). We report subgroup analyses for the final analysis at a median OS follow-up of 18.9 months (olaparib) and 15.5 months (TPC). Patients (N = 302) with gBRCAm, HER2-negative mBC and ≤2 previous lines of chemotherapy for mBC were randomized 2:1 to open-label olaparib (300 mg twice daily) or TPC. All subgroup analyses were prespecified except site of metastases. Investigator-assessed median PFS was 8.0 months (95% confidence interval [CI] 5.8-8.4; 176/205 events) for olaparib and 3.8 months (95% CI 2.8-4.2; 83/97 events) for TPC (hazard ratio 0.51, 95% CI 0.39-0.66). In subgroup analyses, median PFS hazard ratios (95% CI) favored olaparib: hormone receptor status (triple-negative: 0.47, 0.32-0.69; hormone receptor-positive: 0.52, 0.36-0.75); gBRCAm (BRCA1: 0.49, 0.35-0.71; BRCA2: 0.49, 0.33-0.74); site of metastases (visceral/CNS: 0.53, 0.40-0.71; non-visceral: 0.45, 0.23-0.98); prior chemotherapy for mBC (yes: 0.51, 0.38-0.70; no: 0.49, 0.30-0.82); prior platinum-based chemotherapy for BC (yes: 0.49, 0.30-0.83; no: 0.50, 0.37-0.69); progressive disease at randomization (yes: 0.48, 0.35-0.65; no: 0.61, 0.36-1.07). Investigator-assessed objective response rates were higher across all subgroups with olaparib (35-68%) vs TPC (5-40%). Global health status/health-related quality of life increased in all subgroups with olaparib vs decreased/no change with TPC. These data confirm the consistency of olaparib benefit across patient subgroups in OlympiAD.
Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. [2022]Olaparib has single-agent activity against breast/ovarian cancer (BrCa/OvCa) in germline BRCA1 or BRCA2 mutation carriers (gBRCAm). We hypothesized addition of olaparib to carboplatin can be administered safely and yield preliminary clinical activity.
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]In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness of olaparib in similar patients, in a setting reflecting clinical practice.
Olaparib for advanced breast cancer. [2021]Olaparib, an oral PARP-inhibitor, has shown clinical benefit for HER2-negative advanced breast cancer patients carrying a germinal BRCA1/2 mutation. In a randomized Phase III trial, olaparib significantly prolonged progression-free survival as compared with chemotherapy of physician choice. Moreover, in the same trial, a prespecified subgroup analysis reported an overall survival benefit for patients not previously pretreated with chemotherapy for metastatic disease. This review focuses on available preclinical, pharmacokinetic and pharmacodynamic data regarding olaparib and clinical evidence of its antitumor efficacy (both as monotherapy and in combination) and tolerability in breast cancer patients. Open questions, such as use of appropriate biomarkers for patient selection and combination/sequencing with other anticancer drugs, are also addressed.
Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]Olaparib (Lynparza™) is a PARP inhibitor approved for advanced BRCA-mutated (BRCAm) ovarian cancer. PARP inhibitors may benefit patients whose tumours are dysfunctional in DNA repair mechanisms unrelated to BRCA1/2. We report exploratory analyses, including the long-term outcome of candidate biomarkers of sensitivity to olaparib in BRCA wild-type (BRCAwt) tumours.
Olaparib shows promise in multiple tumor types. [2014]A phase II study of the PARP inhibitor olaparib (AstraZeneca) for cancer patients with inherited BRCA1 and BRCA2 gene mutations confirmed earlier results showing clinical benefit for advanced breast and ovarian cancers, and demonstrated evidence of effectiveness against pancreatic and prostate cancers.
Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy.