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Poster session 01

113P - Pembrolizumab in microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) advanced solid tumors: An update of the phase II KEYNOTE-158 trial

Date

10 Sep 2022

Session

Poster session 01

Topics

Clinical Research;  Immunotherapy;  Cancer in Special Situations

Tumour Site

Presenters

Michele Maio

Citation

Annals of Oncology (2022) 33 (suppl_7): S27-S54. 10.1016/annonc/annonc1037

Authors

M. Maio1, P.A. Ascierto2, D. Motola Kuba3, N. Penel4, P.A. Cassier5, G.M. Bariani6, A. De Jesus-Acosta7, T. Doi8, F. Longo Muñoz9, W.H. Miller10, D. Oh11, M. Gottfried12, L. Yao13, F.J. Jin14, A. Gozman15, A. Marabelle16

Author affiliations

  • 1 Medical Oncology, University of Siena and Center for Immuno-Oncology, 53100 - Siena/IT
  • 2 Melanoma, Cancer Immunotherapy & Developmental Therapeutics, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Pascale, 80131 - Napoli/IT
  • 3 Medical Oncology, COMOP A.C., Clinical Investigation, 14050 - Mexico City/MX
  • 4 Medical Oncology, Centre Oscar Lambret and Lille University, 59020 - Lille/FR
  • 5 Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 6 Medical Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, 01246-000 - São Paulo/BR
  • 7 Medical Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 21287 - Baltimore/US
  • 8 Experimental Therapeutics, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 9 Medical Oncology, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 10 Oncology, Jewish General Hospital McGill University, H3T 1E2 - Montreal/CA
  • 11 Internal Medicine, Seoul National University Hospital and Cancer Research Institute, 110-744 - Seoul/KR
  • 12 Oncology, Meir Medical Center, 44281 - Kfar Saba/IL
  • 13 Biostatistics, Merck & Co., Inc., 07065 - Rahway/US
  • 14 Clinical Development, Merck & Co., Inc., 07065 - Rahway/US
  • 15 Clinical Development, Merck & Co., Inc., 07065-0900 - Rahway/US
  • 16 Département D’innovation Thérapeutique Et D’essais Précoces (ditep), Gustave Roussy, Institut National de la Santé et de la Recherche Médicale (INSERM) U1015, Université Paris Saclay, 94805 - Villejuif/FR
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Abstract 113P

Background

Pembrolizumab provides durable tumor responses in patients (pts) with advanced MSI-H/dMMR solid tumors. Data from the multicohort KEYNOTE-158 (NCT02628067) trial supported approval by FDA of pembrolizumab for unresectable or metastatic MSI-H/dMMR advanced solid tumors that progressed on prior therapy. Here we present data from 373 pts with MSI-H/dMMR tumors with a median follow-up approximate of 54 months.

Methods

In this nonrandomized, phase II, open-label trial, pts aged ≥ 18 years (yr) with previously treated, MSI-H/dMMR non colorectal cancers (cohorts A- K) received 200 mg pembrolizumab Q3W for up to 35 cycles, until progression, unacceptable toxicity, or pt/investigator withdrawal. MSI-H/dMMR status was assessed by IHC or PCR. The primary endpoint was ORR per RECIST 1.1 by independent central review. Secondary endpoints were DOR, PFS, OS. The database cut-off date was January 22, 2022.

Results

At data cut-off, a total of 373 pts were enrolled. The most common cancers were endometrial (N=94), gastric (N=51), small intestine (N=26), ovarian (N=25), and biliary tract (N=22). A total of 208 pts (56%) had ≥2 prior lines of therapy. The median duration of follow-up was 53.7 months (range, 14.7-71.4). The overall ORR was 34% (95% CI: 29.0 - 38.8 [11% CR; 23% PR). The ORR for the most common cancers enrolled were: endometrial 50%, gastric 39%, small intestine 58%, ovarian 32% and biliary tract 41%. The median DOR was 63.2 months (range, 1.9+ - 63.9+) for all cohorts with a 3 yr DOR rate of 69%. The median OS was 19.8 months (95% CI: 14.5, 25.8) with 3 yr OS rate of 39%. Median PFS was 4.0 months (95% CI: 2.4-4.3) with 3-yr PFS rate of 25%. Drug-related adverse events (AE) were reported in 248 pts (67%) of whom 50 (13%) had grade ≥3 AEs. Three pts (1%) died due to a drug-related AE of myocarditis, pneumonia, or Guillain-Barre syndrome, in 1 pt each. Immune-mediated AEs were reported in 83 pts (22%) of whom 24 (6%) had grade ≥3 AEs.

Conclusions

Pembrolizumab continues to show robust antitumor activity and generates durable responses in pts with MSI-H or dMMR cancers regardless of tumor type, with a manageable safety profile.

Clinical trial identification

NCT02628067; First posted on Dec. 11, 2015.

Editorial acknowledgement

Editorial assistance provided by Jose Casasnovas Nieves, an employee of the study sponsor, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, 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

M. Maio: Financial Interests, Personal, Advisory Role: BMS, Alfasigma, Pierre Fabre, Novartis, GSK, Amgen, MSD, Merck, Sanofi, Roche, Eli Lilly, Iontura, Sciclone, Incyte; Financial Interests, Personal, Other, travel expenses: BMS, Alfasigma, Pierre Fabre, Novartis, GSK, Amgen, MSD, Merck, Sanofi, Roche, Eli Lilly, Iontura, Sciclone, Incyte; Financial Interests, Personal, Stocks/Shares: Theravance, Epigen Therapeutics. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory Role: Dohme, iTeos; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. D. Motola Kuba: Financial Interests, Personal, Advisory Role: Roche, MSD, Merck, AstraZeneca, Amgen, Ipsen, GSK; Financial Interests, Personal, Speaker’s Bureau: Roche, MSD, Merck, AstraZeneca, Amgen, Ipsen, GSK. N. Penel: Financial Interests, Institutional, Research Grant, Research grant for clinical trials in sarcoma filed: Bayer HealthCare. P.A. Cassier: Financial Interests, Personal, Advisory Board: Merck Serono/EMD, Roche, Amgen; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Advisor: Ose Immunotherapeutics; Financial Interests, Institutional, Invited Speaker: AbbVie, Amgen, Blueprint, Exelixis, GSK, Janssen, Novartis, Roche, Taiho, Loxo/Eli Lilly; Non-Financial Interests, Institutional, Product Samples: Plexxikon, Novartis, MSD, AstraZeneca, GSK. G.M. Bariani: Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Mabxience; Non-Financial Interests, Advisory Role: Libbs. A. De Jesus-Acosta: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme Corp.; Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp., AstraZeneca, Eli Lilly. T. Doi: Financial Interests, Institutional, Research Grant: Eli Lilly, MSD, Daiichi Sankyo, Taiho, Novartis, Merck Biopharma, Janssen Pharmaceutical, Boehringer Ingelheim, Pfizer, BMS, AbbVie, Eisai, Chugai Pharma; Financial Interests, Personal, Advisory Role: Janssen Pharmaceutical, Boehringer Ingelheim, Chugai Pharma, Rakuten Medical, Kanen Pharmaceutical, NanoCarrier, Kyowa Kirin, Takeda Pharmaceutical, Otsuka Pharmaceutical, Shionogi, Sumitomo Pharma, PRA Health Science; Financial Interests, Personal, Invited Speaker: BMS, Ono Pharmaceutical, AstraZeneca, Daiichi Sankyo. F. Longo Muñoz: Financial Interests, Personal, Advisory Role: Amgen, Bayer, Bristol Myers Squibb, Lilly, MSD, Roche, Servier; Financial Interests, Personal, Other, honoraria, travel expenses: Amgen, Bayer, Bristol Myers Squibb, Celgene, Ferrer, Lilly, Merck, MSD, Roche, Sanofi, Servier. W.H. Miller: Financial Interests, Personal, Other, Consultant fees: Merck, BMS, Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, Sanofi; Financial Interests, Personal, Other, Honoraria/speaker's bureau: BMS, Merck; Financial Interests, Personal, Other, Honoraria/Speaker’s Bureau: Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, Sanofi; Financial Interests, Institutional, Research Grant, Grant: Merck, CIHR, CRS, Terry Fox Research Institute, SWCRF, CCSRI; Financial Interests, Institutional, Other, Clinical Trial: Merck, MiMic, Astellas, BMS, Novartis, GSK, Incyte, Pfizer, Sanofi, Ocellaris Pharma, Alkermes, Genentech, Array, Exelixis, VelosBio, Esperas Pharma. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. L. Yao: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp. F.J. Jin: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp., GSK. A. Gozman: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. A. Marabelle: Financial Interests, Personal, Advisory Role: MSD, BMS, Roche/Genentech, AstraZeneca, Sanofi, Pfizer/Merck Serono; Financial Interests, Personal, Funding: Foundation MSD Avenir, BMS, AstraZeneca, Roche/Genentech, Sanofi; Financial Interests, Institutional, Research Grant: MSD, BMS, Roche/Genentech, AstraZeneca, Sanofi, Pfizer/Merck Serono; Financial Interests, Personal, Other, Travel expenses: MSD, BMS, Roche/Genentech, AstraZeneca. All other authors have declared no conflicts of interest.

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