Nivolumab plus ipilimumab (N+I) in patients (pts) with pancreatic cancer (PC) with <i>BRCA1/2</i> mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

715 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results from a cohort of pts with PC with BRCA1/2 mut treated with N+I are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options or prior immune checkpoint inhibitor tx. PD-L1 expression testing was not required. Genomic testing was performed in CLIA-certified, CAP-accredited site-selected labs. Most genomic tests did not distinguish between germline or somatic mut. Pts received I at 3 mg/kg every 3 weeks (wks) for 4 doses with N at 1 mg/kg IV every 3 wks for 4 doses. N alone was then continued at 240 mg every 2 wks or 480 mg every 4 wks until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial (PR) response per RECIST v. 1.1, or stable disease of at least 16 wks duration (SD16+). CR is based on radiographic assessment. CA 19-9 levels were not collected. Simon 2-stage design tested null DC rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled; otherwise, the cohort is closed. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and SD, and safety. DOR is defined as time from pt’s first documented OR to progressive disease. Results: 32 pts with PC with BRCA1 (n=8), BRCA2 (n=22) or both BRCA1/2 (n=2) were enrolled between October 2017 and March 2023. 4 pts were not evaluable for efficacy. Pts had adenocarcinoma (n=29), acinar cell carcinoma (n=2), and poorly differentiated carcinoma (n=1). Table shows demographics and outcomes. 1 CR, 3 PR and 4 SD16+ were observed for a DC rate of 31% (90% CI, 18 to 100) and OR rate of 14% (95% CI, 4 to 33). The pt with CR had a BRCA1 mut, the pts with PR had BRCA1 (n=1) and BRCA2 (n=2) muts, and the pts with SD16+ had BRCA1 (n=2) and BRCA2 (n=2) muts. The null DC rate was rejected (p=0.04). The pt with CR remains on tx with a DOR of 311 wks as of May 2024. 15 pts received prior tx with olaparib and 1 of those pts had SD16+ on this study. 17 pts had ≥1 drug-related grade 3-4 adverse event (AE) or serious AE. All were consistent with N+I labels except generalized muscle weakness and lymphopenia. Conclusions: N+I shows antitumor activity in pts with PC with BRCA1/2 mut and warrants further study. Clinical trial information: NCT02693535 . Demographics (N=32) and efficacy outcomes (n=28). Median (Med) age, years (range) 66 (37-80) ECOG PS, % 0-12 31 (97)1 (3) Prior systemic regimens, % 0-2≥3 10 (31)22 (69) DC rate, % (OR and SD16+) (90% CI) 31 (18, 100) OR rate, % (95% CI) 14 (4, 33) Med PFS, wks (95% CI) 9 (7, 16) Med OS, wks (95% CI) 34 (14, 46)