Nivolumab Plus Ipilimumab in Patients With Solid Tumors With High Tumor Mutation Burden: Results From the Targeted Agent and Profiling Utilization Registry Study.

PURPOSE Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of three cohorts of patients with colorectal cancer (CRC), breast cancer (BC), and other solid tumors (histology-pooled [HP]) with high tumor mutation burden (HTMB) treated with nivolumab plus ipilimumab (N + I) are reported. METHODS Eligible patients had tumors with HTMB (≥10 mutations per megabase), measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was evaluated by a one-sided exact binomial test (α = .10). Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety. RESULTS Patients with CRC (N = 12), BC (N = 13), or other advanced cancers (N = 26) with HTMB were enrolled. The CRC cohort failed to reach the predetermined efficacy threshold to warrant expansion at the end of stage I. The BC cohort expanded to stage II but closed by company request before achieving the planned sample size. The DC rates (one-sided 90% CI) for BC and HP cohorts were 33% (15-100, P = .0976) and 32% (20-100), respectively. The null hypothesized 15% DC rate was rejected for the BC and HP cohorts but not the CRC cohort. Nineteen patients experienced treatment-related grade 3 adverse events (AE) or serious AEs. CONCLUSION N + I demonstrated antitumor activity in patients with tumors with HTMB in the BC and HP cohorts but not the CRC cohort.