1174OPembrolizumab in microsatellite instability high cancers: Updated analysis of the phase II KEYNOTE-164 and KEYNOTE-158 studies

Abstract Background Pembrolizumab (pembro) is indicated for patients (pts) with microsatellite instability-high (MSI-H) solid tumors after 1 prior therapy, and MSI-H colorectal cancer (CRC) after prior fluoropyrimidine, oxaliplatin, and irinotecan, based in part on data showing durable clinical benefit with pembro in the phase II studies KEYNOTE (KN)164 ([NCT02460198] in 61 pts (cohort A) with MSI-H CRC) and KN158 ([NCT02628067] in19 pts with MSI-H non-CRC). Here, we report results of the antitumor activity of pembro in pts with MSI-H tumors from a pooled analysis of KN164 and KN158, with ≥18mo of additional follow-up across 28 tumor types. Methods KN164 enrolled pts with MSI-H CRC (cohort A [≥2 prior], cohort B [≥1 prior therapy]), while KN158 included pts with MSI-H non-CRC (≥1 prior therapy). MSI-H status was determined locally by IHC or PCR or centrally by PCR. Eligible pts in both received pembro 200mg Q3W. Tumor response was assessed every 9 wk. Primary endpoint was ORR by central review per RECIST v1.1. Data cutoff date was Sept 4, 2018 for KN164 and Dec 6, 2018 for KN158. Results At data cutoff, 357 pts (124 with MSI-H CRC, 233 with MSI-H non-CRC) were enrolled. Pts had median age of 59 years (range 20-87) and 350 (98%) had ≥1 prior therapy. Common MSI-H non-CRC tumor types included endometrial (n=49), gastric (n=24), cholangiocarcinoma (n=22), pancreatic (n=22), small intestinal (n=19), ovarian (n=15), brain (n=13), sarcoma (n=9), neuroendocrine (n=7), cervical and prostate (n=6) cancers. Median follow-up was 18.0mo (range 0.1-35.6). Confirmed ORR was 34% (n=121; 95% CI 29-39); 30 (8%) pts had CR. Median DOR was not reached (range 2.9 to 31.3+); 54% of pts had response duration ≥18mo. Median OS was 27.8 months mo (95% CI 21.3 to not reached), with 2-year OS rate of 52%. Median PFS was 4.0mo (95% CI 2.5-4.3) with 2-year PFS rate of 31%. Serious drug-related events occurred in 11 (9%) pts with MSI-H CRC and 18 (8%) pts with MSI-H non-CRC. The safety profile was consistent with that previously seen for pembro. A pooled safety analysis will be presented. Conclusions Pembro provides robust antitumor activity with durable responses and a manageable safety profile in pts with MSI-H cancers independent of tumor type. Clinical trial identification KN164 NCT02460198 KN158 NCT02628067. Editorial acknowledgement Luana Atherly-Henderson, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA. Legal entity responsible for the study Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding Merck & Co., Inc. Disclosure L.A. Diaz: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck & Co., Inc.; Advisory / Consultancy: Caris; Advisory / Consultancy: Lyndra; Advisory / Consultancy: Genocea Biociences; Advisory / Consultancy: Illumina; Advisory / Consultancy: Cell Design Labs; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Neophore; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: PGDx; Officer / Board of Directors: Jounce Therapeutics; Licensing / Royalties: Johns Hopkins; Licensing / Royalties: MSKCC; Spouse / Financial dependant: Amgen. D. Le: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck & Co., Inc.; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Aduro Biotech. M. Maio: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: GSK; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: MedImmune. P.A. Ascierto: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Pierre Fabre, Incyte; Advisory / Consultancy: Genmab; Advisory / Consultancy: Newlink Genetics; Advisory / Consultancy: MedImmune; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Syndax; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Idera; Advisory / Consultancy: Ultimovacs; Advisory / Consultancy: Sandoz; Advisory / Consultancy: Immunocore; Advisory / Consultancy: 4SC. R. Geva: Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy, Educational grant to the research unit - Novartis: Novartis; Honoraria (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution): Lilly; Honoraria (institution): Medison; Honoraria (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution): Janssen; Honoraria (institution): Takeda; Honoraria (institution), Travel / Accommodation / Expenses: Merck & Co., Inc. D. Motola-Kuba: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Asopharma; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: MSD. T. Andre: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: HalioDx; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Servier. E. Van Cutsem: Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Ipsen. J. Delord: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Novartis. D. Jager: Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Advisory / Consultancy: Bayer. T.W. Kim: Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer. R. Guimbaud: Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony: MSD; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Merck & Co., Inc.; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Novartis. T. Yoshino: Research grant / Funding (institution): Novartis K.K.; Research grant / Funding (institution): MSD K.K.; Research grant / Funding (institution): Sumitomo Dainippon Pharma ; Research grant / Funding (institution): Chungai Pharmaceutical; Research grant / Funding (institution): Sanofi K.K.; Research grant / Funding (institution): Daiichi Sankyo Company; Research grant / Funding (institution): PAREXEL International Inc; Research grant / Funding (institution): Ono Pharmaceutical Co. M. Chen: Full / Part-time employment: Merck & Co., Inc. K. Norwood: Full / Part-time employment: Merck & Co., Inc. P. Marinello: Full / Part-time employment: Merck & Co., Inc. A. Marabelle: Advisory / Consultancy: Merck Serono; Advisory / Consultancy: eTheRNA; Advisory / Consultancy: Lytix pharma; Advisory / Consultancy: Kyowa Kirin Pharma; Honoraria (institution), Advisory / Consultancy: Bayer; Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: BMS; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Genmab; Advisory / Consultancy: Amgen; Advisory / Consultancy: Biothera; Advisory / Consultancy: Nektar; Advisory / Consultancy: GSK; Advisory / Consultancy: Oncovir; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Flexus Bio; Advisory / Consultancy: Roche/Genentech; Honoraria (institution), Speaker Bureau / Expert testimony: Roche; Honoraria (institution): Pierre Fabre; Honoraria (institution): Onxeo; Honoraria (institution): EISAI; Honoraria (institution): Genticel; Honoraria (institution): Rigontec; Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Imaxio; Honoraria (institution): Sanofi; Honoraria (institution): BioNTech. All other authors have declared no conflicts of interest.