795MO - Pembrolizumab (pembro) in patients (pts) with microsatellite instability-high (MSI-H) advanced endometrial cancer (EC): Updated results from KEYNOTE-158

Background

Treatment options for previously treated, advanced MSI-H or mismatch repair deficient (dMMR) tumors are limited. Pembro showed durable and clinically meaningful benefit in previously treated, advanced MSI-H/dMMR tumors, including EC, in the nonrandomized, open-label, phase II KEYNOTE-158 study (NCT02628067). ORR of 57% was observed in 49 pts with MSI-H/dMMR EC in KEYNOTE-158. We present longer follow up in more pts from KEYNOTE-158.

Methods

Pts from cohorts D (EC, regardless of MSI-H status) and K (any MSI-H/dMMR solid tumor, except colorectal) were ≥18 y, had previously treated, advanced MSI-H/dMMR EC, measurable disease per RECIST v1.1, ECOG PS 0/1 and provided a tumor sample for biomarker analysis. In cohort D, MSI-H expression was determined retrospectively by PCR at a central lab. In cohort K, MSI-H/dMMR output was determined prospectively by PCR and/or IHC at a local lab, respectively. Pts received pembro 200 mg Q3W for up to 35 cycles. Primary endpoint was ORR per RECIST v1.1 by independent central radiologic review. Secondary endpoints included DOR, PFS, OS, and safety. Efficacy was assessed in pts who received ≥1 pembro dose and had ≥26 wk follow up; and safety in all treated pts.

Results

As of Oct 5, 2020, 18/90 pts (20%) had completed 35 cycles of pembro and 52 (58%) had discontinued treatment. In the efficacy population (n = 79), median time from first dose to data cutoff was 42.6 (range, 6.4–56.1) mo; 41 (52%) had ≥2 lines of prior therapy and 61% had ECOG PS 1. ORR was 48%, with DOR ≥3 y in 68%; see the table for results. 68/90 pts (76%) had treatment-related AEs (grade 3–4, 12%; no grade 5), and led to discontinuation in 7%. 25 pts (28%) had immune-mediated AEs and infusion reactions (grade 3–4, 7%; no grade 5).

Conclusions

Pembro demonstrated robust and durable ORR (48%; CR, 14%), encouraging survival outcomes and manageable toxicity in pts with heavily pretreated, advanced MSI-H/dMMR EC, and is a promising treatment option in this setting. Table: 795MO

Clinical trial identification

NCT02628067.

Editorial acknowledgement

Writing support was provided by Christabel Wilson, MSc, of ICON plc (North Wales, PA, USA), funded by Merck Sharp & Dohme Corp., 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 Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, BBI, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance Biotherapeutics, Inc, Myriad Genetics, Eisai, Agenus, Tarveda, Merck & Co., Inc., Kenilworth, NJ, USA, SeaGen, Novart; Financial Interests, Institutional, Funding: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc., Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, NCI, Bristol Mye. G.M. Bariani: Financial Interests, Personal, Funding: Mabxience; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Libbs. P.A. Cassier: Financial Interests, Personal, Funding: Roche/Genentech; Novartis; Amgen; Bristol Myers Squibb; Blueprint Medicines; GlaxoSmithKline; Janssen; Eli Lilly; Taiho Pharmaceutical; AstraZeneca; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Celgene; AbbVie; Toray ; Financial Interests, Personal, Other, Personal fees: Roche/Genentech; Novartis; Amgen; Merck Serono; and AstraZeneca; Non-Financial Interests, Personal, Other, Nonfinancial support: Roche/Genentech; Novartis; AstraZeneca; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; and Plexxikon; Financial Interests, Personal, Other, Travel accommodations: Netris Pharma. A. Marabelle: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD); Financial Interests, Personal, Other, Honorarium: MSD; Financial Interests, Personal, Research Grant: Fondation de l’Avenir and Bristol Myers Squibb; Financial Interests, Speaker’s Bureau: Bristol Myers Squibb and MSD. A.R. Hansen: Financial Interests, Personal, Advisory Role: Genentech/Roche, Merck & Co., GSK, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, MedImmune; Financial Interests, Personal, Funding: Genentech/Roche, Merck & Co., GSK, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, MedImmune, Boston Medical. A. De Jesus Acosta: Financial Interests, Personal, Funding: AstraZeneca; Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Other, Consultancy: Merck & Co., Inc., Kenilworth, NJ, USA. W.H. Miller, Jr: Financial Interests, Personal, Other, Personal fees for serving as a consultant: BMS, Merck & Co., Inc., Kenilworth, NJ, USA, Roche, Novartis, Amgen, GSK, and Sanofi. A. Italiano: Financial Interests, Personal, Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; AstraZeneca; Merck Serono; and Bayer; Financial Interests, Personal, Other, Personal fees: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; AstraZeneca; Bayer; Bristol Myers Squibb; Epizyme; and Roche. L. Xu: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA. F. Jin: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA. K. Norwood: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA. M. Maio: Financial Interests, Personal, Advisory Board: Roche; Bristol Myers Squibb; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Incyte; AstraZeneca; Amgen; Pierre Fabre; Eli Lilly; GlaxoSmithKline; Sanofi; Alfasigma; Merck Serono; Financial Interests, Personal, Other, Honoraria: Roche, Bristol Myers Squibb; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; AstraZeneca; Amgen; Pierre Fabre; Eli Lilly; GlaxoSmithKline; Sciclone; Sanofi; Alfasigma; Merck Serono; Financial Interests, Personal, Stocks/Shares: Epigen Therapeutics, and Theravance. All other authors have declared no conflicts of interest.