Nivolumab plus ipilimumab (N+I) in patients (pts) with colorectal cancer (CRC) with BRCA1/2 alterations (alts): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with genomic alts. Results in a cohort of pts with CRC with mutation (mut) or deletion (del) treated with N+I are reported. 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 muts. 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 or partial (PR) response per RECIST v. 1.1, or stable disease (SD) of at least 16 wks duration (SD16+). 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 I 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 and SD, and safety. 33 pts with CRC and mut (n=5), mut (n=20), del (n=7), or del and mut (n=1) were enrolled from October 2017 to September 2023. 3 pts were not evaluable for efficacy. Table shows demographics and outcomes. 1 PR ( del) and 4 SD16+ (all mut) were observed for a DC rate of 24% (90% CI, 9 to 100) and OR rate of 3% (95% CI, <1 to 17). The null DC rate failed to be rejected (p=0.33). Microsatellite instability or high tumor mutational burden were not detected in pts with DC. 12 pts (36%) had ≥1 tx-related grade 3-4 adverse event (AE) or serious AE. All were consistent with tx labels except: encephalopathy, generalized muscle weakness, hypophosphatemia, hypotension, INR increase, leukocytosis, proteinuria, and sinus tachycardia. N+I did not meet prespecified criteria to declare a signal of activity in pts with CRC with alts. Other tx should be considered for these pts, including tx offered in clinical trials. .

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics