Pembrolizumab therapy for microsatellite instability high (MSI-H) colorectal cancer (CRC) and non-CRC.

3071 Background: Mismatch repair deficient cancers harbor high levels of microsatellite instability and somatic mutations. Treatment with anti-PD-1 antibodies has resulted in durable objective responses in MSI-H cancer. As part of the ongoing, global, multicenter phase 2 studies KEYNOTE(KN)164 and KN158, we assessed the efficacy of pembrolizumab in patients (pts) with MSI-H tumors. Methods: Both studies enrolled pts with MSI-H status determined locally by IHC or PCR. KN164 enrolled pts with MSI-H CRC and ≥2 prior therapies, whereas the multicohortKN158 study included pts with MSI-H non-CRC and ≥1 prior therapy. Eligible pts in both studies received pembrolizumab 200 mg Q3W until progression, unacceptable toxicity, or pt/investigator decision. Tumor response was assessed every 9 wk by independent review per RECIST v1.1. Primary endpoint was ORR. Secondary endpoints included DOR, PFS, OS, and safety. Analyses were performed in pts from KN164 and KN158 who had ≥27 wk of follow-up as of Aug 3, 2016 and Oct 19, 2016, respectively. Results: KN164 enrolled 61 pts with MSI-H CRC (90% with ≥2 prior therapies) whereas KN158 included 21 pts with MSI-H non-CRC (42% with ≥2 prior therapies). In KN158 the most common tumor types were endometrial and small intestinal cancer (n = 4 each), cholangiocarcinoma (n = 3), and gastric and pancreatic cancer (n = 2 each). Median follow-up was 7.4 mo for MSI-H CRC and 4.5 mo for MSI-H non-CRC. ORR for MSI-H CRC was 26.2% (95% CI, 15.8%-39.1%), with 15 confirmed responses and 1 unconfirmed response, and ORR for MSI-H non-CRC was 42.9% (21.8%-66.0%), with 8 confirmed responses and 1 unconfirmed response. DCR was 50.8% (n = 31; 37.7%-63.9%) for MSI-H CRC and 66.7% (n = 14; 38.4%-83.7%) for MSI-H non-CRC. Median duration of response was not reached for either MSI-H CRC or non-CRC, and 100% of responses were ongoing. Survival and safety analyses are ongoing. Conclusions: Early results from KN164 and KN158 confirm the robust antitumor activity of pembrolizumab in heavily pretreated pts with MSI-H cancers. Clinical trial information: NCT02628067; NCT02460198.