Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two-year clinical update.

Abstract

4040 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC. Clinical trial information: NTC02060188 . [Table: see text]