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Poster display session

5340 - Efficacy of pembrolizumab in phase 2 KEYNOTE-164 and KEYNOTE-158 studies of microsatellite instability high cancers

Date

11 Sep 2017

Session

Poster display session

Presenters

Luis Diaz

Citation

Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367

Authors

L. Diaz1, A. Marabelle2, T.W. Kim3, R. Geva4, E. Van Cutsem5, T. André6, P.A. Ascierto7, M. Maio8, J. Delord9, M. Gottfried10, R. Guimbaud11, D. Jaeger12, E. Elez13, T. Yoshino14, A. Joe15, B. Lam16, J. Ding15, S. Pruitt17, S..P. Kang16, D.T. Le18

Author affiliations

  • 1 Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York City/US
  • 2 Département D’innovation Thérapeutique Et D’essais Précoces, Gustave Roussy, Université Paris-Saclay, Villejuif/FR
  • 3 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 4 Research Unit, Division Of Oncology, Tel Aviv Sourasky Medical Center, 64239 - Tel Aviv/IL
  • 5 Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, 3000 - Leuven/BE
  • 6 Medical Oncology, Hopital Saint Antoine, 75571 - Paris/FR
  • 7 Melanoma, Cancer Immunotherapy And Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, 80131 - Naples/IT
  • 8 Oncology, Azienda Ospedaliera Universitaria Senese - Santa Maria delle Scotte, 53100 - Siena/IT
  • 9 Clinical Research Unit, Institut Universitaire du Cancer -Toulouse- Oncopole, 31059 - Toulouse/FR
  • 10 Oncology, Meir Medical Center, 44281 - Kfar Saba/IL
  • 11 Department Of Gastroenterology And Oncology, CHU Rangueil, Toulouse/FR
  • 12 Oncology, National Center for Tumor Diseases, Heidelberg/DE
  • 13 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 14 Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 15 Clinical Research, Merck & Co., Inc., Kenilworth/US
  • 16 Medical Oncology, Merck & Co., Inc., Kenilworth/US
  • 17 Oncology Early Development, MSD - Merck & Co USA, 07033 - Kenilworth/US
  • 18 Medical Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/US
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Resources

Abstract 5340

Background

A high level of microsatellite instability (MSI-H) is indicative of a tumor deficient in mismatch repair (dMMR). Prior reports suggest that anti-PD-1 antibody therapy provides durable responses in patients (pts) with MSI-H cancers. Here we assessed efficacy of PD-1 blockade using pembrolizumab in pts with dMMR/MSI-H (hereafter termed MSI-H) advanced cancer enrolled in two ongoing, global, multicenter phase 2 studies KEYNOTE (KN)164 and KN158. We report results in 61 pts with MSI-H CRC and 77 pts with MSI-H non-CRC across 20 tumor types.

Methods

KN164 enrolled pts with MSI-H colorectal cancer (CRC) and ≥2 prior therapies, whereas the multicohort KN158 study included pts with MSI-H non-CRC and ≥1 prior therapy. MSI-H status was determined locally by IHC or PCR or centrally by PCR. Eligible pts in both studies received pembrolizumab 200 mg Q3W. Tumor response was assessed every 9 wk. Primary endpoint was ORR by independent central review per RECIST v1.1. Database cut-off date was Feb 10, 2017 for KN164 (≥54 wk follow-up) and Jan 27, 2017 for KN158 (≥27 wk follow-up).

Results

KN164 enrolled 61 pts with MSI-H CRC (90% with ≥2 prior therapies) and KN158 enrolled 77 pts with MSI-H non-CRC (52% with ≥2 prior therapies), at data cutoff. Tumor types represented in KN158 in at least 2 pts included endometrial (n = 17), gastric (n = 11), small intestinal (n = 10), pancreatic (n = 9), biliary (n = 8), mesothelioma and small cell lung (n = 3 each), adrenocortical, bladder, and thyroid (n = 2 each) cancers. ORR was 27.9% (n = 17 [all confirmed]; 95% CI 17.1%-40.8%) for MSI-H CRC and 37.7% (n = 29 [23 confirmed and 6 unconfirmed]; 95% CI 26.9%-49.4%) for MSI-H non-CRC. Median DOR was not reached for MSI-H CRC (range 2.9+ to 12.5+) or MSI-H non-CRC (range 2.4+ to 9.2+). Median OS was not reached for either MSI-H CRC or MSI-H non-CRC, with 6-mo OS rates of 87% and 73%, respectively.

6-mo PFS rates were 43% for MSI-H CRC and 45% for MSI-H non-CRC. 4 (7%) pts with MSI-H CRC and 7 (9%) with MSI-H non-CRC had serious drug-related AEs. The safety profile was consistent with that previously seen for pembrolizumab.

Conclusions

Pembrolizumab provides robust antitumor activity with durable responses in heavily pretreated pts with MSI-H cancers.

Clinical trial identification

ClinicalTrials.gov NCT02460198. MK-3475 164 First received: May 29, 2015 Last updated: February 16, 2017 Last verified: February 2017 AND ClinicalTrials.gov NCT02628067. MK-3475 158 First received: December 9, 2015 Last updated: February 23, 2017 Last verified: February 2017

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Disclosure

L. Diaz: Travel expenses from Merck & Co., Inc. A. Marabelle: Advisory board for Merck Serono, eTheRNA, Lytix pharma, Kyowa Kirin Pharma, Bayer, Novartis, Bristol-Myers Squibb, Symphogen, Genmab, Amgen, Biothera, Nektar, GSK, Oncovir, Pfizer, Seattle Genetics, Flexus Bio, Roche-Genentech. Speakers’ bureau for MSD. T.W. Kim: Advisory board member for Amgen. Research funding from Taiho, Bayer. R. Geva: RG: Advisory board member for Bayer, MSD & Novartis. Honoraria from Bristol-Myers Squibb, Lilly, Medison, Roche, Novartis and Janssen. E. Van Cutsem: Research funding from Amgen, Bayer, Boehringer, Celgene, Ipsen, Lilly, MSD, Merckserono, Novartis, Roche, Sanofi and Servier. T. André: Honoraria from Bohrigner Ingenheim, Merck, Serono, Baxter, Bayer and Roche. P.A. Ascierto: Advisory board member for Bristol-Myers Squibb, Roche-Genentech, MSD, Novartis, Array, Amgen, Merck Serono, and Pierre Fabre. M. Maio: Honoraria, travel expenses and consulting fees from Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, GSK, & Medimmune. R. Guimbaud: Advisory board member for Novartis. Travel expenses, including accommodations from Roche, Ipsen, Lilly and Sanofi. D. Jaeger: Consulting or advisory roles and Roche, Bristol-Myers Squibb & Bayer. T. Yoshino, A. Joe, B. Lam, J. Ding, S. Pruitt, S.P. Kang: SPK is employed by Merck & Co., Inc. and may own stock options in the company. D.T. Le: Research grants and honoraria from Merck & Co., Inc. All other authors have declared no conflicts of interest.

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