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Clinical Trial
. 2024 Nov;25(6):987-996.
doi: 10.1007/s40257-024-00885-w. Epub 2024 Oct 8.

Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study

Laurent Mortier  1 , Lisa Villabona  2 , Ben Lawrence  3 , Ana Arance  4 , Marcus O Butler  5 , Marie Beylot-Barry  6 , Philippe Saiag  7 , Mahtab Samimi  8 , Paolo A Ascierto  9 , Francesca Spada  10 , Michel De Pontville  11 , Michele Maio  12 , Alfonso Berrocal  13 , Enrique Espinosa  14 , Jaume Capdevila  15 , Max Levin  16 , Debasmita Das  17 , Clemens Krepler  17 , Dmitri Grebennik  17 , Vanna Chiarion-Sileni  18
Affiliations
Clinical Trial

Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study

Laurent Mortier et al. Am J Clin Dermatol. 2024 Nov.

Abstract

Background: The phase III KEYNOTE-913 study was conducted to evaluate the efficacy and safety of pembrolizumab as first-line therapy in patients with advanced Merkel cell carcinoma (MCC).

Objective: The aim was to report results from the primary analysis of KEYNOTE-913.

Patients and methods: Patients with recurrent locally advanced or metastatic MCC received pembrolizumab 200 mg intravenously every 3 weeks for up to 35 treatments (~ 2 years). The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary end points were duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety and tolerability.

Results: Fifty-five patients were treated with pembrolizumab. The median time from first dose to data cutoff (February 15, 2024) was 50.3 months (range 38.7-59.4). The ORR was 49% (95% confidence interval [CI] 35-63), with 12 complete responses and 15 partial responses. The median DOR was 39.8 months (range 4.8-52.5+), and the 24-month DOR rate was 69%. The median PFS was 9.3 months (95% CI 3-26), and the 24-month PFS rate was 39%. The median OS was 24.3 months (95% CI 12.4 to not reached), and the 24-month OS rate was 51%. Any-grade treatment-related adverse events (AEs) occurred in 38 patients (69%); 13 patients (24%) experienced grade 3-5 AEs. The most common treatment-related AEs were fatigue (n = 12 [22%]), pruritus (n = 12 [22%]), and lipase increase (n = 10 [18%]). One patient died of treatment-related Guillain-Barré syndrome.

Conclusions: Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or metastatic MCC, supporting its use in this population.

Trial registration: Clinicaltrials.gov, NCT03783078.

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Conflict of interest statement

Laurent Mortier has received consulting fees and travel support from MSD, BMS, Novartis, and Pierre Fabre. Lisa Villabona, Marie Beylot-Barry, Francesca Spada, Michel De Pontville, and Enrique Espinosa declare that they have no conflicts of interest that might be relevant to the contents of this article. Ben Lawrence has received honoraria and travel support from MSD. Ana Arance has received research funding from MSD, honoraria from MSD and Merck Serono, and travel support from MSD and BMS. Marcus O. Butler has received research funding from Merck, Takara Bio, and Novartis; consulting fees from Bristol Myers Squibb, Merck, Novartis, Adaptimmune, Immunocore, GlaxoSmithKline, Sanofi, Sun Pharma, Instil Bio, IOVANCE, Pfizer, Ideaya Bio, Medison, LaRoche Possey, and Regeneron; and honoraria from Sanofi, Bristol Myers Squibb, Merck, Pfizer, and Novartis; and has participated on a safety review committee for Adaptimmune and GlaxoSmithKline. Philippe Saiag has received research funding and consulting fees from Merck Serono. Mahtab Samimi has received research funding from SOTIO and travel support from BMS and MSD, has participated on advisory boards for Merck and Pfizer, and is chair of EADV. Paolo A. Ascierto has received research support from Bristol Myers Squibb, Roche-Genentech, Pfizer, and Sanofi; consulting fees from Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, Sun Pharma, Sanofi, Sandoz, Italfarmaco, Nektar, Pfizer, Lunaphore, Medicenna, Bio-Al Health, ValoTx, RepImmune, and Bayer; and travel support from Pfizer, Bio-AI Health, and RepImmune; and has participated on advisory boards for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, AstraZeneca, Boehringer Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Oncosec, Nouscom, Seagen, iTeos, and Erasca. Michele Maio has received consulting fees, honoraria, and travel support from, and has participated in advisory boards for, BMS, Roche, MSD, Merck, Sanofi, GSK, AstraZeneca, Pierre Fabre, Alfasigma, Eli Lilly, Amgen, Sciclone, Incyte, and Ionctura; and owns stock in Epigen and Teravance. Alfonso Berrocal has received consulting fees from MSD and BMS and honoraria and travel support from MSD. Jaume Capdevila has received research funding from Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications, Eisai, Amgen, and Bayer; and consulting fees from Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Huchinson Pharma, ITM, Advanz, Merck Serono, Esteve, and Roche. Max Levin has received lecturing fees from Bristol Myers Squibb, Roche, and Merck Sharp & Dohme. Debasmita Das is an employee of Merck & Co., Inc., Rahway, NJ, USA. Clemens Krepler is an employee of, and owns stock in, Merck & Co., Inc., Rahway, NJ, USA. Dmitri Grebennik is an employee of Merck & Co., Inc., Rahway, NJ, USA. Vanna Chiarion-Sileni has received travel support from Pierre-Fabre and Sanofi; has participated on advisory boards for Pierre-Fabre and Merck Sharp & Dohme.

Figures

Fig. 1
Fig. 1
Trial profile
Fig. 2
Fig. 2
Forest plot of ORR in subgroups per RECIST v1.1 by BICR. BICR blinded independent central review, CI confidence interval, ECOG PS Eastern Cooperative Oncology Group performance status, MCC Merkel cell carcinoma, ORR objective response rate, RECIST v1.1 Response Evaluation Criteria in Solid Tumors, version 1.1
Fig. 3
Fig. 3
Best percentage change from baseline in the sum of target lesions per RECIST v1.1 by BICRa. BICR blinded independent central review, RECIST v1.1 Response Evaluation Criteria in Solid Tumors, version 1.1. aIncludes all patients with at least 1 postbaseline assessment
Fig. 4
Fig. 4
Kaplan-Meier estimates of DOR per RECIST v1.1 by BICR (A), PFS per RECIST v1.1 by BICR (B), and OS (C). BICR blinded independent central review, CI confidence interval, DOR duration of response, mo months, NR not reached, OS overall survival, PFS progression-free survival, RECIST v1.1 Response Evaluation Criteria in Solid Tumors, version 1.1
See this image and copyright information in PMC

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