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

5548 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 in a cohort of pts with OC with BRCA1/2 mut treated with N+I are reported. Methods: Eligible pts had advanced OC, measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was done in CLIA-certified, CAP-accredited labs. PD-L1 status was not routinely reported. Pts received I at 3 mg/kg every 3 wks for 4 doses with N at 1 mg/kg IV every 3 weeks (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 or partial (PR) response per RECIST v. 1.1, or stable disease of at least 16+ wks duration (SD16+). CA-125 levels were not routinely reported. Simon 2-stage design tested the 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. P-value calculated based on 2-stage design. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: 33 pts with OC and BRCA1 (n=20), BRCA2 (n=10), or both mut (n=3) were enrolled from Sept 2017 to Oct 2019. 6 pts were not evaluable for efficacy analysis; 1 pt was found to be ineligible after enrolling, 5 pts discontinued tx before the post-baseline tumor evaluation due to an adverse or serious adverse event (SAE). Table shows demographics and efficacy outcomes. 6 pts with PR were observed for an OR rate of 22% (95% CI: 9% to 42%) and a DC rate of 27% (90% CI: 13% to 36%); the null hypothesis of a 15% DC rate was not rejected (p=0.17). 3 pts with PR had BRCA1 mut only, 2 pts had BRCA2 mut only and 1 pt had both BRCA1 and BRCA2 mut. Of the 6 pts with PR, 4 had microsatellite (MS) stable (MSS) tumors and MS status was not reported in 2. Of the 4 with MSS, 3 had a tumor mutational burden (TMB) ≤ 10 mutations per megabase and 1 had TMB of 11. 11 pts had at least 1 tx-related SAE, including acute kidney injury, ALT/AST increase, colitis, dehydration, diarrhea, E. coli, electrolyte disorder, fever, nausea/vomiting and pneumonitis. Conclusions: N+I did not meet prespecified criteria to declare a signal of activity in pts with OC and BRCA1/2 mut. However, given 22% of pts had PR (2 with >1 year duration) in this heavily pretreated cohort, additional study may be warranted to further evaluate efficacy. Clinical trial information: NCT02693535 . [Table: see text]

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics