Phase 2 trial of pembrolizumab and olaparib (POLAR) maintenance for patients (pts) with metastatic pancreatic cancer (mPDAC): Two cohorts B non-core homologous recombination deficiency (HRD) and C exceptional response to platinum-therapy.

• DOI: 10.1200/jco.2023.41.16_suppl.4140
• Publication Date: 2023-06-04T15:37:26Z
• Authors: Wungki Park; Catherine O'Connor; Joanne F. Chou; Carly Schwartz; Anna M. Varghese; Mary Larsen; Fiyinfolu Balogun; Robin Brenner; Kenneth H. Yu; Erin Diguglielmo; Shigeaki Umeda; Elias Karnoub; Fergus Keane; Haochen Zhang; Smita Suhas Joshi; Nadeem Riaz; David Paul Kelsen; Marinela Capanu; Christine A Iacob...; Eileen Mary O'Reilly
• Keywords: Olaparib

4140 Background: Maintenance olaparib improves PFS in g BRCA1/2m (core HRD) mPDAC (Golan, NEJM 2019). Whether other HRD indicators, such as gene mutations than (non-Core HRD, Cohort B) and exceptional platinum responders (Cohort C, response > 6 months) may benefit from PARPi remains unanswered. We hypothesized that pembrolizumab (POLAR) combination improve outcome by immunogenic cell death. Methods: conducted an open-label, non-randomized, phase 2 trial of POLAR maintenance therapy for pts with whose disease had not progressed 4 months (m) B or m C. Herein, we report on Cohorts & Eligibility: ECOG 0-1, meeting eligibility (Pembrolizumab 200mg IV Q3W+ OLApaRib 300mg BID) until progression limiting toxicity. Objective rate (ORR), median (mPFS), overall survival (mOS), control (DCR), CA 19-9, cfDNA baseline mutational signature were analyzed. Results: C enrolled N=15 each. N=25 evaluable RECIST 1.1. Median follow-up 9.9 (1.3-22.8) 11.3 (5.8-23) m, respectively. Efficacy details are shown. G3-5 AEs related to treatment: 5/14 (36%): 1 diarrhea (7%), hyperglycemia anemia (14%), lipase increased (7%). B: 9/15 (60%) ATM, 3 CHEK2, MUTYH, BLM, FANCC. Canonical less common B, especially ATM PA group (n=9) vs genomic instability score (GIS) was computed higher 28 (0-38) 9 (0-24) p=0.052. tumor mutation burden (TMB) different between (3.3 4.1). Conclusions: Clinical activity observed select Although modest (mPFS 4m [2.1-5.4] + C), intriguing signal (mOS at 14m [10-NR] first dose) seen patients without chemotherapy. Extensive correlative analyses underway evaluate resistance (SPORE: 1P50CA257881-01A1). A actively accruing. information: NCT04666740 . [Table: see text]