EA2192 / APOLLO – A Randomized Phase II Double-Blind Study of Olaparib versus Placebo Following Adjuvant Chemotherapy in Patients with Resected Pancreatic Cancer and a Pathogenic BRCA1, BRCA2 or PALB2 Mutation

Biological subsets of pancreatic cancer are an increasingly recognized phenomenon. However, treatment in the curative-intent setting has yet to be tailored to subsets of patients based on their tumor profiles. Approximately 4%-8% of all pancreatic cancers may be driven by a pathogenic mutation in BRCA1, BRCA2, or PALB2. Research suggests the addition of PARP inhibitors to standard multimodal treatment may be beneficial in this setting and that the earlier in the treatment course these agents are used, the more effective they appear to be.

Against this backdrop, the newly opened APOLLO study (EA2192) will explore whether the addition of maintenance PARP inhibition for BRCA- or PALB2-mutated pancreatic cancer improves outcomes. Investigators posit that pancreatic adenocarcinoma that develops in the setting of one of these germline mutations may represent a biologically unique group that may benefit from tailored perioperative management.

Patients may be eligible for this phase II double-blind study if they have successfully undergone curative intent pancreatic cancer resection and have no evidence of residual disease. They must be receiving, planning to receive, or be within eight weeks of having completed standard perioperative chemotherapy (neoadjuvant, adjuvant, or a combination of both). They must have a pathogenic germline or somatic mutation in BRCA1, BRCA2, or PALB2, per local testing before registration.

Participants will be randomized 2:1 to either the experimental arm for twice-daily 300-mg olaparib (n=102) or to the placebo arm (n=50) for 12 four-week cycles. Patients will be further stratified based on three factors: R1 vs. R0 resection, receipt of platinum vs. non-platinum perioperative chemotherapy, and neoadjuvant vs. adjuvant therapy.

The study’s primary objective is to determine the relapse-free survival benefit from the addition of maintenance olaparib after completion of chemotherapy. All patients will be followed for response until progression and for survival for ten years.

This study is led by Kim A. Reiss BInder, MD (University of Pennsylvania).

Learn more about EA2192 at ecog-acrin.org.