Phase II KEYNOTE-164 study of pembrolizumab (pembro) monotherapy for patients (pts) with previously treated, mismatch repair–Deficient (dMMR) advanced colorectal cancer (CRC): Primary and Japan subgroup analyses

Abstract

Background: A high level of microsatellite instability (MSI-H) and abnormal expression of MMR proteins is indicative of a dMMR tumor. Prior reports suggest that anti-PD-1 antibody therapy provides durable responses in pts with dMMR cancers. We report primary outcomes from cohort A and the Japan subgroup of the KEYNOTE-164 study of pts with dMMR CRC (NCT02460198). Method(s): Pts with metastatic CRC previously treated with standard therapies (fluoropyrimidine, oxaliplatin, and irinotecan), with dMMR or MSI-H confirmed locally by IHC or PCR, were enrolled. Eligible pts received pembro 200 mg Q3W for 2 years or until progression, unacceptable toxicity, or withdrawal of consent. Tumor response was assessed every 9 weeks per RECIST v1.1 by independent review. The primary end point was objective response rate (ORR); secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Data cutoff was Feb 10, 2017. Result(s): Of 61 pts enrolled, median age was 53 y in the overall cohort and 51 y in the Japan subgroup; 59% and 43% were male, respectively. Most pts received 2 prior (46% and 29%) or >= 3 prior (44% and 71%) lines of therapy. Median duration of follow-up was 13.2 mo (range, 0.2-16.9) in the overall cohort and 13.2 mo (8.0-16.9) in the Japan subgroup. In the overall cohort, ORR was 28% (17 PR; 95% CI, 17-41), DCR was 51% (95% CI, 38-64), and median DOR was NR (range, 2.9+ to 12.5+ mo). The 12-mo PFS and OS rates were 34% and 72%. In the Japan subgroup (n = 7), ORR was 29% (2 PR; 95% CI, 4-71), DCR was 57% (95% CI, 18-90), and median DOR was NR (range, 10.2+ to 10.4+ mo); 12-mo PFS and OS rates were 29% and 57%. Treatment-related AEs occurred in 35/61 (57%) and 5/7 (71%) of the overall cohort and Japan subgroup. Immune-mediated AEs and infusion reactions occurred in 11/61 (18%) and 2/7 (29%), respectively. There were no treatment-related deaths. Conclusion(s): Pembro provided durable antitumor activity in heavily pretreated pts with dMMR CRC in the overall cohort and Japan subgroup, with a safety profile consistent with that previously observed for pembro.