Phase II study of ipilimumab and nivolumab (ipi/nivo) in metastatic uveal melanoma (UM).

Abstract

9522 Background: UM is the most common primary intraocular malignant tumor in adults. Approximately 40-50% of patients (pts) with UM will ultimately develop metastatic disease. There is currently no standard approach for metastatic UM. Early studies of single agent immunotherapy (IO) in metastatic UM have yielded meager results. Combination checkpoint inhibitor IO has the potential to improve response rates and survival. Herein, we report the safety and efficacy of ipi/nivo in metastatic UM. Methods: We performed a single-arm phase II study in metastatic UM (CA184-187) for pts with at least 1 measureable lesion and ECOG PS 0-1. Any number of prior treatments were permitted. Pts received nivolumab 1mg/kg IV plus ipilimumab 3mg/kg IV every 3 weeks for a total of 4 doses; maintenance nivolumab was dosed 3mg/kg every 2 weeks or 480mg IV every 4 weeks. The primary efficacy endpoint was best overall response rate (BORR) as determined by irRC. Secondary endpoints were median progression free survival (PFS), median overall survival (OS), and one-year OS. Results: As of the January 31, 2019 data cutoff, 39 pts were enrolled. 35 pts received at least one treatment and were evaluable for toxicity. 5 pts were inevaluable for response due to lack of follow-up imaging, leaving 30 pts evaluable for efficacy. 32 pts (91%) experienced any adverse event (AE), and 29 pts (83%) experienced any treatment related AE (TRAE). Grade 3-4 TRAEs occurred in 14 pts (40%). 10 pts (29%) were removed from the study due to AEs. There were no treatment-related deaths. Median duration of follow up is 60.5 weeks. 19 pts (63%) completed all 4 cycles of ipi/nivo; median duration of treatment was 16 weeks. The BORR was partial response for 5 pts (17%), stable disease (SD) for 16 pts (53%), and progression of disease for 9 pts (30%). 8 pts had SD for at least 6 months. Median PFS was 26 weeks. Median OS was 83 weeks (1.6 years), and one-year OS was 62%. Conclusions: Full results of ipi/nivo safety and efficacy including immune-related AE and clinical characteristics of the responders will be presented at the meeting. Preliminary translational tumor work including RNA analysis has been performed on a subset of responders. Clinical trial information: NCT01585194.