Pembrolizumab in Patients with Advanced Miscellaneous Rare Cancers: Results from a Phase 2 Basket Trial.

Introduction: Rare solid tumors account for one-quarter of cancers among adults in the United States, but few resources have been devoted to their treatment. We evaluated the efficacy of pembrolizumab, a programmed cell death-1 inhibitor, in patients with rare solid tumors. Methods: We conducted a phase 2 basket trial that included patients with rare, advanced tumors. Patients were enrolled in the study in nine tumor-specific and a 10th cohort of miscellaneous rare histologies. Patients received pembrolizumab 200 mg intravenously every 21 days. The primary endpoint was the non-progression rate at 27 weeks per immune-related Response Evaluation Criteria in Solid Tumors (RECIST). The secondary endpoints were confirmed objective response (immune-related complete response [irCR] or partial response [irPR]), clinical benefit (irCR, irPR, or immune-related stable disease [irSD] ≥ 4 months), safety, and tolerability. Pretreatment biopsy specimens were examined for programmed cell death ligand-1 combined positive score (CPS) and tumor-infiltrating lymphocyte status. Herein, we report the outcomes in 12 patients with miscellaneous rare histologies who were on the study between October 5, 2016, and August 30, 2019. Results: Twelve patients with rare cancers were enrolled from October 5, 2016, to August 30, 2019. The patients received a median of four lines of therapy before enrollment. Three patients (25%) remained free of progression at 27 weeks, one patient (8%) had an objective response, and five patients (42%) received clinical benefit. Six patients (50%) experienced at least one adverse event, of whom five (42%) experienced immune-related adverse events. The only grade ≥ 3 adverse event was non-immune-related anemia. Among the seven patients with CPS ≥ 1, one had irPR and two had irSD as the best response. Among the six patients with a CPS of 3, one had irPR and two had irSD as the best response. Conclusions: Single-agent pembrolizumab showed modest efficacy and was well tolerated in patients with rare solid tumors (ClinicalTrials.gov Identifier: NCT02721732).