Pembrolizumab + Olaparib for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+366 other locations
Overseen ByVincent Chung
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial studies whether adding pembrolizumab to olaparib (standard of care) works better than olaparib alone in treating patients with pancreatic cancer with germline BRCA1 or BRCA2 mutations that has spread to other places in the body (metastatic). BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. These proteins help repair damaged deoxyribonucleic acid (DNA) and, therefore, play a role in ensuring the stability of each cell's genetic material. When either of these genes is mutated, or altered, such that its protein product is not made or does not function correctly, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to some types of cancer, including pancreatic cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Olaparib is an inhibitor of PARP, a protein that helps repair damaged DNA. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. The addition of pembrolizumab to the usual treatment of olaparib may help to shrink tumors in patients with metastatic pancreatic cancer with BRCA1 or BRCA2 mutations.
How is the drug combination of Pembrolizumab and Olaparib unique for treating pancreatic cancer?
The combination of Pembrolizumab and Olaparib is unique because it combines an immune checkpoint inhibitor (Pembrolizumab) with a PARP inhibitor (Olaparib), which targets cancer cells with specific genetic mutations, offering a novel approach compared to traditional chemotherapy for pancreatic cancer.
12378What data supports the effectiveness of the drugs Pembrolizumab and Olaparib for pancreatic cancer?
Some evidence suggests that Pembrolizumab and Olaparib may help certain patients with advanced pancreatic cancer, especially those with specific genetic markers like dMMR or BRCA2 mutations. In a few cases, patients treated with these drugs showed no cancer progression for several months to years.
34689Will I have to stop taking my current medications?
The trial requires that you stop taking strong or moderate CYP3A inhibitors or inducers at least 2 to 5 weeks before starting olaparib. Check with your doctor to see if your current medications fall into these categories.
Is the combination of Pembrolizumab and Olaparib safe for humans?
Olaparib has been studied for safety in various cancers, including ovarian and breast cancer, and is generally considered safe, though it may have side effects like nausea and fatigue. Pembrolizumab, also known as KEYTRUDA, is used in many cancer treatments and is generally safe, but can cause side effects like fatigue and skin reactions.
23579Eligibility Criteria
This trial is for adults with metastatic pancreatic cancer who have inherited BRCA mutations. They must have completed first-line platinum-based chemotherapy, show stable or responding disease, and not be on certain drugs that affect olaparib. People with HIV or hepatitis C can join if treated and virus-free. Those with a history of severe lung inflammation, active infections, autoimmune diseases needing recent treatment, or other cancers that could interfere are excluded.Inclusion Criteria
I have been diagnosed with pancreatic adenocarcinoma.
I am 18 years old or older.
I have never been treated with immune checkpoint inhibitors.
I have never needed steroids for non-infectious lung inflammation.
I have metastatic disease and have received first line platinum-based chemotherapy.
I do not have an infection that needs treatment with medication.
I have not been diagnosed with immunodeficiency or taken high-dose steroids or immunosuppressants in the last week.
I can carry out all my usual activities without help.
I have a hereditary BRCA 1 or 2 mutation confirmed by a certified lab.
I have never been treated with PARP inhibitors.
I can swallow pills and don't have stomach issues affecting medicine absorption.
Participant Groups
The study is testing if adding pembrolizumab (an immunotherapy drug) to olaparib (a PARP inhibitor used as standard care) is more effective in treating patients whose pancreatic cancer has spread and have BRCA1/2 mutations. It's a phase II trial where the effectiveness of this combination will be compared to using olaparib alone.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A (olaparib, pembrolizumab)Experimental Treatment6 Interventions
Patients receive olaparib PO BID on days 1-21 and pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 19, patients receive olaparib PO BID on days 1-42 and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI, tumor biopsy and blood sample collection throughout the study.
Group II: Arm B (olaparib)Active Control5 Interventions
Patients receive olaparib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI, tumor biopsy and blood sample collection throughout the study.
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:
Marshfield Clinic Stevens Point CenterStevens Point, WI
Illinois CancerCare-CantonCanton, IL
IHA Hematology Oncology Consultants-CantonCanton, MI
McFarland Clinic PC - AmesAmes, IA
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Olaparib: first global approval. [2020]Olaparib (Lynparza™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by AstraZeneca for the treatment of solid tumours. The primary indication that olaparib is being developed for is BRCA mutation-positive ovarian cancer. A capsule formulation of the drug has received approval for use in this setting in the EU and USA, and a tablet formulation is in global phase III trials (including in the USA, EU, Australia, Brazil, Canada, China, Israel, Japan, Russia and South Korea). In addition, phase III trials in breast, gastric and pancreatic cancer are underway/planned, and phase I/II investigation is being conducted in other malignancies, including prostate cancer, non-small cell lung cancer, Ewing's sarcoma and advanced cancer. This article summarizes the milestones in the development of olaparib leading to this first approval for ovarian cancer.
Olaparib in combination with irinotecan, cisplatin, and mitomycin C in patients with advanced pancreatic cancer. [2022]Olaparib is an oral inhibitor of polyadenosine 5'-diphosphoribose polymerization (PARP) that has previously shown signs of activity in patients with BRCA mutations and pancreatic ductal adenocarcinoma (PDAC).
Clinical Activity and Safety of Cediranib and Olaparib Combination in Patients with Metastatic Pancreatic Ductal Adenocarcinoma without BRCA Mutation. [2022]Cediranib and olaparib combination did not result in clinically meaningful activity in patients with metastatic pancreatic ductal adenocarcinoma without known BRCA mutation.
Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer. [2022]Previous findings showed that cediranib-olaparib increased PFS in women with recurrent platinum-sensitive ovarian cancer compared to olaparib alone.
Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [2022]To systematically evaluate the efficacy and safety of olaparib in the treatment of recurrent platinum-sensitive ovarian cancer.
Survival Benefit of Pembrolizumab for Patients With Pancreatic Adenocarcinoma: A Case Series. [2022]Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with 5-year survival rate of 10%. Evidence about pembrolizumab usage for PDAC is limited even though it is Food and Drug Administration (FDA)-approved for treatment of advanced pancreatic cancer with deficient mismatch repair expression (dMMR) or high tumor mutational burden (TMB) where as there is limited evidence for programmed death-ligand 1 (PD-L1)-positive PDACs. We present three patients with different stages of advanced PDAC treated with pembrolizumab as single maintenance therapy or combination with other therapy. Case 1 is a patient with borderline resectable PDAC, treated with neoadjuvant chemotherapy and surgical resection, followed with pembrolizumab as maintenance therapy with no progression for 4 years after test showed patient was dMMR positive. Case 2 is a patient who was found to have locally advanced PDAC, treated with neoadjuvant chemotherapy and surgical resection followed by multiple line of treatment with programmed cell death-1 (PD-1) and breast cancer gene 2 (BRCA2)-positive status treated with pembrolizumab and olaparib maintenance without any evidence of progression for more than 3 years. Case 3 is a patient with metastatic PDAC with PD-1 and BRCA2-positive status initially treated with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) and gemcitabine plus nab-paclitaxel switched to irinotecan liposomal, at the same time was started on maintenance pembrolizumab and olaparib with no progression on computed tomography (CT) surveillance for 8 months. For patient with different stages of PDAC with dMMR mutation or PD-1 expression, pembrolizumab should be explored more as maintenance therapy for patients with surgical operable PDAC to decrease recurrence, or as a combination with targeted therapy or chemotherapy to prolong survival in patients with advanced PDAC.
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.
Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. [2023]Pembrolizumab confers minimal benefit to most patients with pancreas cancer. We explored survival and patient treatment burden (for example, death within 14 days of therapy) in a subgroup who had early access to pembrolizumab .
A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations. [2023]To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects.