Outcomes of Patients with Rare Cancers Treated with Combination Immune Checkpoint Inhibitors With and Without Prior anti-PD-1/L1 Exposure (NCI/SWOG S1609).

Background: There are limited data on response and survival outcomes for patients who receive the combination of anti-PD-1 and anti-CLTA-4 after prior failure of an anti-PD-1/L1, in particular among patients with less common cancers. We analyzed a unique trial resource, an NCI-sponsored basket trial for participants with rare solid tumors conducted by SWOG that was open at over 1,000 sites across the USA (S1609/DART). Participants received Ipilimumab (1mg/kg every six weeks) plus nivolumab (240 mg every two weeks) (both intravenously). The trial eligibility allowed prior exposure to anti-PD-1/L1, and our objective was to compare response and survival outcomes for patients with and without prior anti-PD-1/PDL-1. Methods: Logistic and Cox regression models were used to evaluate associations between prior anti-PD-1/PDL-1 exposure and the endpoints of clinical benefit rate (CBR) (includes stable disease of at least six months and objective response by RECISTv1.1), progression-free survival (PFS), and overall survival (OS). Results: CBR was not significantly different between those with and without prior anti-PD-1/L1 exposure, 26% in both groups. There were no significant differences in PFS and OS between patients with and without prior anti-PD-1/L1 exposure on either univariate and multivariable analysis (multivariable hazard ratio, 95% confidence interval and p-value: PFS: 1.18, 0.83-1.68, p=0.36; OS: 1.11, 0.76-1.63, p=0.58). Conclusions: There were no statistically or clinically significant differences in outcomes with and without prior anti-PD-1/L1 exposure for patients with a variety of rare cancers treated with nivolumab and ipilimumab. Patients with prior anti-PD-1/L1 exposure should be eligible for clinical trials evaluating combination immunotherapy.