LBA7 - Pembrolizumab versus chemotherapy in microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC): 5-year follow-up of the KEYNOTE-177 study Asia subgroup

Background

Pembrolizumab (pembro) provided durable responses and fewer treatment-related adverse events (TRAEs) vs chemotherapy (chemo) in patients (pts) with MSI-H/dMMR mCRC in KEYNOTE-177 (NCT02563002), including pts enrolled in Asia (Taiwan, S Korea, Singapore, Japan). These results supported approval of pembro as 1L therapy in these regions. We report data from a 5-year follow-up of pts enrolled in Asia.

Methods

Eligible pts aged ≥18 y with MSI-H/dMMR mCRC measurable per RECIST v1.1 and an ECOG PS of 0 or 1 were randomly assigned 1:1 to receive 1L pembro 200 mg IV Q3W for ≤35 cycles or chemo (mFOLFOX6 or FOLFIRI ± bevacizumab or cetuximab). Pts who received chemo could crossover to ≤35 cycles of pembro after centrally confirmed PD. End points were OS and PFS (primary), safety (secondary), and DOR (exploratory).

Results

At data cutoff (July 17, 2023), median follow-up (range) was 74.2 mo (6.2y; 66.9-86.6) in the pembro arm and 72.8 mo (6.1y; 65.5-83.9) in the chemo arm. A total of 22/153 pts assigned to pembro and 26/154 assigned to chemo were enrolled in Asia. All pts in the pembro arm and 25/26 pts in the chemo arm received treatment. 11/26 pts (42%) in the chemo arm crossed over to pembro per protocol. Median OS (95% CI) was not reached (NR; 13.8-NR) with pembro and 30.0 mo (2.5y; 14.7-NR) with chemo (HR 0.62, 95% CI 0.27-1.41). 5-yr OS rates were 59% and 42%, respectively. In the global population after 5y of follow-up, median OS (95% CI) was 77.5 mo (6.5y; 49.2- NR) with pembro vs 36.7 mo (3.1y; 27.6-65.3) with chemo (HR 0.73, 95% CI 0.53-0.99). 5-y OS rates were 55% and 44%, respectively. In the Asia subgroup, TRAEs occurred in 14/22 pts (64%) in the pembro and 100% of pts in the chemo arms. Grade 3-4 TRAEs occurred in 2 pts (9%) and 20 pts (80%), respectively. No pts died due to a TRAE. PFS and DOR per RECIST v1.1 by BICR will be reported.

Conclusions

With 5 y of follow-up, clinical benefit of 1L pembro for MSI-H/dMMR mCRC in the Asian subgroup appears durable and consistent with the global population of KEYNOTE-177. Fewer grade 3-4 TRAEs occurred with pembro vs chemo. These data further support pembro as 1L therapy for pts with MSI-H/dMMR mCRC.

Clinical trial identification

NCT02563002; September 29, 2015.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Mehak Aggarwal, PharmD, and Matthew J. Grzywacz, PhD, of ApotheCom (Yardley, PA, USA).

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd., Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd. T. André: Financial Interests, Personal, Advisory Board, Advosiry Board on February 12, 2021: Astellas pharma; Financial Interests, Personal, Advisory Board, Advisory Board on February 2021: Kaleido Biosciences; Financial Interests, Personal, Invited Speaker, and advisory board 2021: Amgen; Financial Interests, Personal, Invited Speaker, Ivited speaker in a symposuim december 2020: AstraZeneca; Financial Interests, Personal, Advisory Board, and consultant fees and consultant contract 2021 and 2022: Bristol MyersSquibb; Financial Interests, Personal, Advisory Board, Advisory board in Janaury 2020: Clovis; Financial Interests, Personal, Advisory Board, Advisory board in january 2020: Gritstone Oncology; Financial Interests, Personal, Advisory Board, Advisory board 2020: Haliodx; Financial Interests, Personal, Advisory Board, and consultant fees/consultant contract and invited speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker, and other: Pierre Fabre; Financial Interests, Personal, Invited Speaker, in an symposuim in 2020: Roche; Financial Interests, Personal, Invited Speaker, in a meeting in 2019: Ventana; Financial Interests, Personal, Invited Speaker, In a educational meeting in 2019: Sanofi; Financial Interests, Personal, Advisory Board, in a symposuim in 2020: Servier; Financial Interests, Personal, Advisory Board, Consultant with personnal fees and invited speaker: Servier; Financial Interests, Personal, Advisory Board, in 2019: GSK; Financial Interests, Personal, Invited Speaker, in 2020 and 2021: GSK; Financial Interests, Personal, Invited Speaker, Virtual symposuimLecture: 1 MSI-H CRC: Implementation of Immunotherapy in clinical practice (30 minutes) – (this will be pre-recorded)Q&A – Live Q&A – (10 minutes) (on July 2, 2021): MSD Oncology; Financial Interests, Personal, Invited Speaker, June 2022: Sanofi; Financial Interests, Personal, Advisory Board, Contract 2021, 2022, 2023: Merck & Co., Inc.; Financial Interests, Personal, Advisory Board, Contrat 2019, 2020, 2021, 2022: BMS; Financial Interests, Personal, Advisory Board, Contract 2021: Gritstone Oncologie; Financial Interests, Personal, Invited Speaker, June 2022 and June 2023 during ESMO GI meeting: Seagen; Financial Interests, Personal, Writing Engagement, Contract of consulting 2021 and 2022 and 2023: MSD Oncology; Financial Interests, Personal, Advisory Board, September 2022: GSK, Seagen; Financial Interests, Personal, Writing Engagement, Contract of consulting 2022 and 2023: GSK; Financial Interests, Personal, Writing Engagement, Contract of consulting 2022: Nordic Pharma; Financial Interests, Personal, Invited Speaker, October 2022: Merck Serono; Financial Interests, Personal, Other, Educationnal in 2022: Roche; Financial Interests, Personal, Other, Contract of consulting 2020, 2021, 2022,2023: Servier; Financial Interests, Personal, Advisory Board, Gilead Sciences Global GI Advisory Board on January 18, 2023: Aptitude Health, Glilead; Financial Interests, Personal, Other, Consultant like member of the SGNTUC-029 Steering Committee (the “Steering Committee”) Services related to the Company’s Study titled “An Open-label Randomized Phase 3 Study of Tucatinib in Combination with Trastuzumab and mFOLFOX6 versus mFOLFOX6 given with or without either Cetuximab or Bevacizumab as First-line Treatment for Subjects with HER2+ Metastatic Colorectal Cancer” (collectively, the “Services”). Including teleconferences and board preparation befor the board (6h)Participation of the Board on September 2022 in Paris, September 10, 2022 MOUNTAINEER-03 Steering Committee Meeting during ESMO: Seagen; Financial Interests, Personal, Other, Consultant like member of the to be a member of the Colorectal Program Scientific Advisory Committee (SAC). In charges for reviewing V940 Pembro on Engagezone (as per your contract in ref).and also an inrtview about Pembrolizumab for MSI/dMMR Metastaic colo-rectal 2023: MSD Oncology; Financial Interests, Personal, Advisory Board, but also formation for the takeda team, and consultant for TakedaContract beetween 1 sept 2023 and 15 october 2024: Takeda; Financial Interests, Personal, Advisory Board, Board Meeting (October 19, 2023): AbbVie; Financial Interests, Institutional, Coordinating PI, PI Garnet study: GSK; Financial Interests, Institutional, Coordinating PI, Keynote 164 and 171 and 811 and C08: MSD; Financial Interests, Institutional, Coordinating PI, BMS CA209-8HW, BMS CA209-142, BMS CA209-577: BMS; Financial Interests, Institutional, Coordinating PI, SPOTLIGHT study: Astellas; Financial Interests, Personal, Steering Committee Member, and internationnal PI (trial chair Solstice study): Servier; Financial Interests, Personal, Steering Committee Member, MOUNTAINEER and MOUNTAINEER-03 study (PI for France) 2022, 2023: Seagen; Financial Interests, Institutional, Local PI, A Randomized, Open-Label, Phase 2 Study of Botensilimab (AGEN1181) as Monotherapy and in Combination with balstilimab (AGEN2034) or Investigator’s Choice Standard of Care (regorafenib or trifluridine and tipiracil) for the Treatment of Refractory Metastatic Colorectal Cancer: Agenus; Non-Financial Interests, Personal, Member of Board of Directors, Investigator: Gercor group; Non-Financial Interests, Personal, Member of Board of Directors, President since october 2022: ARCAD Foundation. T.W. Kim: Financial Interests, Institutional, Research Grant: Genentech. W.P. Yong: Financial Interests, Personal, Invited Speaker: DKSH Singapore Pte Ltd., AstraZeneca Singapore Pte Ltd., Bristol Myers Squibb (S) Pte Ltd., MSD Pharma (Singapore) Pte Ltd., Novartis (S) Pte Ltd.; Financial Interests, Personal, Advisory Board: Ipsen Pharma Singapore Pte Ltd., Amgen; Financial Interests, Institutional, Local PI: Novartis (S) Pte Ltd., Amgen. K. Shiu: Financial Interests, Personal, Invited Speaker, Educational Webinars on CRC and UGI cancer management with immunotherapy: BMS; Financial Interests, Personal, Advisory Board, Advisory Board on Regorafenib for chemorefractory mCRC in readiness for NICE application: Bayer; Financial Interests, Personal, Invited Speaker, Educational webinars on Pembrolizumab for MSI-High CRC, as well as OG cancers: MSD; Financial Interests, Personal, Advisory Board, For Pembrolizumab in CRC of OG cancers pre or NICE application or post NICE approval: MSD; Financial Interests, Personal, Invited Speaker, Webinars on updates on management of mCRC: Merck Serono; Financial Interests, Personal, Advisory Board, On Mirati GI Global Advisory Board: Mirati Therapeutics; Financial Interests, Personal, Invited Speaker, To update company on indications/updates in landscape of immunotherapy and vaccines in GI cancers: Nouscom; Financial Interests, Personal, Advisory Board, Advisory on Cancer of Unknown Primary, new indications of molecular profiling using Foundation Medicine 1: Roche; Financial Interests, Personal, Advisory Board, Advisory Board on Lonsurf for chemorefractory mCRC in readiness for NICE application: Servier; Financial Interests, Institutional, Local PI, For MATTERHORN Trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator on KEYNOTE 177, KEYNOTE 859, KEYNOTE 811, LEAP 17, MK1308A-008 trials: MSD; Financial Interests, Institutional, Research Grant, Chief Investigator of investigator initiated, MSD funded NEOPRISM-CRC trial: MSD; Financial Interests, Institutional, Local PI, UCLH PI for LEAP 15 and MK4280A-007 trials: MSD; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for NOUS209-001 trial: Nouscom; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for CUPSICO trial: Roche; Financial Interests, Personal, Steering Committee Member, Steering Committee Member of CUPISCO trial: Roche; Non-Financial Interests, Personal, Member: ASCO, Association of Cancer Physicians UK. L.H. Jensen: Non-Financial Interests, Institutional, Principal Investigator: 2cureX, BMS, MSD, Roche, Pfizer. C.J.A. Punt: Financial Interests, Institutional, Advisory Board: Nordic Pharma. R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Bayer, BMS, HMP, Ipsen, Merck, Midatech, MSD, Novartis, PharmaMar, Pierre Fabre, Servier; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Personal, Leadership Role, Global PI of investigator-initiated clinical trials (AXINET, NICENEC, PEMBROLA): BMS, MSD, Pfizer; Other, Personal, Other, Honoraria received by spouse for advisory board or invited speaker roles: Abbie, AstraZeneca, Bayer, Boehringer, BMS, Genomica, Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. J. Alcaide-Garcia: Financial Interests, Personal, Invited Speaker, Travel/Accommodations/Expenses: Merck, Amgen, Servier; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Sanofi, MSD; Financial Interests, Personal, Invited Speaker: Pierre-Fabre. P. Gibbs: Financial Interests, Personal, Advisory Board: Merck, Bayer, Amgen, Servier, Haystack Oncology; Financial Interests, Personal, Invited Speaker: MSD. C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai, Servier, MSD, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Pierre Fabre Oncologie, Servier; Non-Financial Interests, Personal, Principal Investigator: Amgen, Daichi Sankyo, MSD. F. Rivera: Financial Interests, Personal and Institutional, Invited Speaker: MSD, Amgen, Roche, BMS, AstraZeneca, Servier, Bayer; Financial Interests, Personal and Institutional, Research Grant: MSD, Amgen, Roche, BMS, AstraZeneca, Servier, Bayer; Financial Interests, Personal and Institutional, Funding: MSD, Amgen, Roche, BMS, AstraZeneca, Servier, Bayer; Financial Interests, Personal and Institutional, Principal Investigator: MSD, Amgen, Roche, BMS, AstraZeneca, Servier, Bayer; Financial Interests, Personal and Institutional, Advisory Board: Amgen, Roche, BMS, AstraZeneca, Servier, Bayer. M.E. Elez Fernandez: Financial Interests, Personal, Advisory Board: Hoffman La - Roche, Servier, Amgen, Merck Serono, Sanofi, Bayer, Pierre Fabre, MSD, Takeda; Financial Interests, Personal, Invited Speaker: Organon, Novartis, Pfizer; Financial Interests, Personal, Other, Educational training: Seagen International GmbH; Financial Interests, Institutional, Funding: Hoffmann-La Roche Ltd., Sanofi Aventis Recherche & Développement, Amgen Inc., Boehringer Ingelheim, Novartis Farmacéutica SA, Bristol Myers Squibb International Corporation, BeiGene, HalioDX SAS, Janssen-Cilag SA, Merck Health KGAA, Merck Sharp & Dohme de España SA, PharmaMar SA, Servier, Taiho Pharma USA Inc., Hutchison MediPharma International, Menarini, Merus NV, Pfizer, Mirati, Array Biopharma Inc., AstraZeneca Pharmaceuticals LP, Celgene International SARL, Debiopharm International SA, Genentech Inc., MedImmune; Non-Financial Interests, Personal, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: Sociedad Española de Oncología Médica (SEOM); Non-Financial Interests, Personal, Other, Speaker of the ESMO Academy: European Society for Medical Oncology (ESMO); Non-Financial Interests, Personal, Other, Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy: American Society of Clinical Oncology (ASCO); Other, Personal, Other, Travel, accommodations, expenses.: Roche, Merck Serono, Sanofi, Amgen, Array BioPharma, Servier, Bristol Myers Squibb. D.T. Le: Financial Interests, Personal and Institutional, Invited Speaker: Merck; Financial Interests, Personal and Institutional, Advisory Board: Merck, BMS, Nouscom; Financial Interests, Personal and Institutional, Research Grant: Merck, BMS, Nouscom; Financial Interests, Personal and Institutional, Funding: Merck, BMS, Nouscom; Financial Interests, Personal and Institutional, Principal Investigator: Merck, BMS, Nouscom; Financial Interests, Personal, Advisory Board: GI Therapeutics, Regeneron, Merus; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Personal, Principal Investigator: Regeneron; Financial Interests, Institutional, Research Grant: Curegenix, AbbVie; Financial Interests, Institutional, Principal Investigator: Curegenix, AbbVie; Non-Financial Interests, Institutional, Research Grant: Medivir; Non-Financial Interests, Institutional, Funding: Medivir; Non-Financial Interests, Institutional, Principal Investigator: Medivir. Y. Zuo: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. D. Fogelman, D.E. Adelberg: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. L. Diaz: Financial Interests, Personal, Member of Board of Directors: Quest Diagnostics, Epitope; Financial Interests, Personal, Other, Consultant: PetDx, Innovatus CP, Se'er, Delfi, Blackstone, Kinnate, Neophore; Financial Interests, Personal, Other, Holds equity: Quest Diagnostics, Epitope, PetDx, Se'er, Delfi, Kinnate, Neophore; Financial Interests, Personal, Other, Spouse holds equity: Amgen. All other authors have declared no conflicts of interest.