112P - Pembrolizumab vs chemotherapy in patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: Asia subgroup results of the phase III KEYNOTE-177 study

Background

KEYNOTE-177 (NCT02563002) was a randomized, open-label phase III study of first-line (1L) pembrolizumab (P) vs chemotherapy (C) in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). P significantly improved progression-free survival (PFS) vs C in KEYNOTE-177; the Asia subgroup (sg) analysis is presented.

Methods

Pts with previously untreated dMMR/MSI-H stage IV mCRC and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned 1:1 to P 200 mg every 3 weeks or investigator’s choice of C (mFOLFOX6/FOLFIRI every 2 weeks ± bevacizumab/cetuximab). Primary endpoints were PFS per Response Evaluation Criteria in Solid Tumors version 1.1 by central review and overall survival. Hazard ratio and 95% confidence interval of PFS were based on Cox regression model with Efron’s method of tie handling with treatment as a covariate. PFS and duration of response (DOR) were assessed per Kaplan-Meier analysis. Secondary endpoints were overall response rate (ORR) and safety. Confirmed responses are shown.

Results

Of 307 pts enrolled in the study, 153 were randomly assigned to P and 154 to C. Of the 307 pts, 48 were enrolled from Asia (P, n=22; C, n=26). At data cutoff (19 Feb 2020), median follow-up in the Asia sg was 28.7 mo in the P arm vs 23.3 mo in the C arm. Efficacy and safety in the total population (pop) and Asia sg are presented in the table.

Conclusions

1L P compared with C showed clinically meaningful improvement in PFS, led to more durable responses and improved safety profile in the total pop of pts with dMMR/MSI-H mCRC. The Asia sg results were generally consistent with those of the total pop of KEYNOTE-177 Table: 112P

APAT, all patients as treated; NR, not reached; TRAE, treatment-related adverse event.

Clinical trial identification

NCT02563002.

Editorial acknowledgement

Provided by Jemimah Walker, PhD, and Doyel Mitra, PhD, of the ApotheCom pembrolizumab team (Yardley, PA). This assistance was 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

T. Yoshino: Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Amgen K.K., Parexel International Inc., MSD K.K., Daiichi Sankyo Co., Ltd., and Sanofi K.K. T.W. Kim: Research grant/Funding (institution): Research Grant/Funding (Institution) Merk Serono, AstraZeneca, Pfizer. W.P. Yong: Speaker Bureau/Expert testimony: Bayer. K-K. Shiu: Honoraria (self): BMS, Guardant Health, Innovent Biologics, Merck KGaA, Roche, Servier; Advisory/Consultancy: Roche; Research grant/Funding (institution): Amgen, BMS, Gilead, Merck KGaA, MSD, Roche; Travel/Accommodation/Expenses: MSD, Merck KGaA, Innovent Biologics. B. Vittrup Jensen: Research grant/Funding (institution): Merck Sharp & Dohme Corp. L. Henrik Jensen: Research grant/Funding (institution): MSD, 2cureX, Incyte, BMS. R. Garcia-Carbonero: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AAA, Advanz Pharma, Bayer, BMS, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Pfizer, Pierre Fabre, Roche, Sanofi and Servier; Research grant/Funding (self): Pfizer, BMS; Research grant/Funding (institution): ARMO Biosciences, AstraZeneca, Pfizer, Novartis, Ipsen, Roche, Pharmacyclics, Boston Biomedicals, Merck, MSD, Amgen, Sanofi, Bayer, Bristol-Myers-Squibb, Boerhringer, Sysmex, Gilead Sciences, Servier, Adacap, VCN, Lilly, Pharmamar; Non-remunerated activity/ies: Member of the Executive Committee of the Spanish Neuroendocrine Tumor Cooperative Group (GETNE), Member of the Executive Committee of the European Society of Neuroendocrine Tumors (ENETS), Member of the Scientific Advisory Group for Oncology (SAG-O) of th; Non-remunerated activity/ies: Global PI of a clinical trial of Axitinib (Pfizer) in NETs; Global PI of a clinical trial of Nivolumab (BMS) and chemotherapy in NECs; Non-remunerated activity/ies: Member of the EORTC, ASCO, ESMO, SEOM, TTD, GEMCAD. J. Alcaide-Garcia: Speaker Bureau/Expert testimony: Amgen; Travel/Accommodation/Expenses: MSD, Merck, Roche, Sanofi, Bristol. P. Gibbs: Honoraria (self), Research grant/Funding (self): Merck. C. de la Fouchardiere: Advisory/Consultancy: Roche, Pierre Fabre Oncologie, MSD, Eisai, Bayer; Travel/Accommodation/Expenses: Amgen, Eisai, BMS, Roche. F. Rivera: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD, Roche, Merck-Serono, Sanofi, BMS, Servier, Lilly, Amgen, Bayer, Celgene. E. Elez: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Hoffman La Roche, Sanofi Aventis, Amgen, Merck Serono, Servier, MSD, Array Pharmaceuticals, Bristol-Myers Squibb; Honoraria (institution): Hoffman La Roche, Sanofi Aventis, Amgen, Merck Serono, MSD, Boehringer Ingelheim, AbbVie, Array Pharmaceuticals, Pierre-Fabre, Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Medimmune. J. Bendell: Research grant/Funding (institution): Gilead, Genentech/Roche, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, EMD Serono, Taiho, Macrogenics, GSK, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Koltan, SynDevRex, Forty Seven, AbbVie, Ar; Advisory/Consultancy: Gilead, Genentech/Roche, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, Taiho, Macrogenics, GSK, Novartis, OncoMed, LEAP, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Array, Sanofi, ARMO, Ipsen, Merrimack, Oncogenex, FORM; Travel/Accommodation/Expenses: Gilead, Genentech/Roche, BMS, Lilly, Merck, MedImmune, Celgene, Taiho, Novartis, OncoMed, BI, ARMO, Ipsen, Oncogenex, FORMA. D.T. Le: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution): Aduro, Medivir, Curegenix, Nouscom; Licensing/Royalties: Patent pending: technology for mismatch repair deficiency. P. Yang: Full/Part-time employment: MSD China Holding Co., Ltd.. M. Farooqui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. P. Marinello: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. L.A. Diaz: Advisory/Consultancy: Personal Genome Diagnostics, 4Paws, Neophore; Leadership role: Jounce Therapeutics, Personal Genome Diagnostics; Shareholder/Stockholder/Stock options: Jounce Therapeutics, Personal Genome Diagnostics, 4Paws, Amgen, Thrive; Research grant/Funding (self), Non-remunerated activity/ies: Merck; Travel/Accommodation/Expenses: Jounce Therapeutics, Personal Genome Diagnostics, 4Paws, Merck, Neophore; Licensing/Royalties: Personal Genome Diagnostics, Thrive, Qiagen; Officer/Board of Directors: Jounce Therapeutics, Personal Genome Diagnostics. T. Andre: Honoraria (self): Bristol-Myers Squibb, Chugai, GSK, Pierre Fabre, Roche/Vantana, Sanofi, Servier ; Advisory/Consultancy: Amgen, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Gritstone Oncology, Halliodx, Merck Sharp & Dohme Corp, Pierre Fabre, Roche/Vantana, Sanofi, Servier, Tesaro; Speaker Bureau/Expert testimony: Bristol-Myers Squibb, Servier; Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Travel/Accommodation/Expenses: Roche/Vantana, Merck Sharp & Dohme Corp, Bristol-Myers Squibb; Non-remunerated activity/ies: Participant to the Scientific committee of ARCAD Foundation and GERCOR Group. All other authors have declared no conflicts of interest.