Pembrolizumab and Olaparib for People With Metastatic Pancreatic Cancer with Homologous Recombination Deficiency or Exceptional Response to Platinum Chemotherapy

About the Study

This is a study for people diagnosed with metastatic pancreatic cancer with Homologous Recombination Deficiency, or whose disease has responded well to first-line or second-line platinum therapy. The goal of this study is to look at whether combining the immunotherapy drug, pembrolizumab and the PARP inhibitor, olaparib is a more effective treatment for this cancer than taking olaparib alone.

Type of Study

The study is an open-label, non-randomized study with three treatment groups. 

• The study is non-randomized. Participants will be assigned to one of three study groups based on specific biomarkers found in the tumor and/or response to platinum chemotherapy.
• The study is open-label. All participants will know which of the groups they have been assigned to. 

Study participants whose cancer is stable or responded responded to first-line or second-line platinum therapy will be divided into three groups:

• Group A: Patients with either inherited mutations or acquired mutations (found in the tumor) in BRCA1, BRCA2, or PALB2.
• Group B: Patients with either inherited mutations or acquired mutations (found in the tumor) in ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, or RTEL1.
• Group C: Patients without any of the gene mutations included in Groups A and B, or patients with variants of unknown significance (VUS) whose cancer is platinum sensitive (had partial or complete response to platinum chemotherapy).

What the Study Entails

Patients in all three study groups will receive the following treatments:

• Pembrolizumab (200 mg) via intravenous (IV) every 3 weeks for 8 cycles. At the start of cycle 9, patients will receive Pembrolizumab (400 mg) via IV every 6 weeks.
• Olaparib (300 mg) twice per day (orally) each day, continuously.

Therapy will continue as long as the cancer does not get worse and patients are tolerating treatment. 

Study Site

New York, NY: Memorial Sloan Kettering Cancer Center
Contact: Wungki Park, MD by phone at 646-888-4543 or by email.      

Men or women age 18 years or older can participate if they:  

• Have either stable disease or responding disease on first-line or second-line platinum therapy for metastatic disease.
• Have metastatic pancreatic cancer with homologous recombination gene alterations or platinum sensitivity, and meet one of the following two criteria:
  • Have either germline or somatic gene mutations in BRCA1, BRCA2, ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, or RTEL1, or
  • Do not have any of the gene mutations listed in the prior bullet, but have platinum-sensitivity. NOTE: Patients with variants of unknown significance (VUS) who demonstrate platinum sensitivity can be considered eligible for this study.
• Had a recurrence after curative surgery, if the recurrence is > 6 months after the last date of adjuvant therapy.
• Are postmenopausal or not pregnant.

Patients will be excluded if they have:  

• Had disease progression on either a first-line or second-line platinum therapy for metastatic pancreatic cancer
• More than one primary cancer (Contact the study team to review a list of exceptions)
• Myelodysplastic syndrome/acute myeloid leukemia
• Symptomatic uncontrolled brain metastases.
• An immunocompromised system, such as those with HIV
• Active Hepatitis B or C, or active tuberculosis (TB)
• Had prior treatment with any PARP inhibitor, including olaparib.