Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial.

BACKGROUND

Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC).

PATIENTS AND METHODS

KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab.

RESULTS

Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients.

CONCLUSIONS

The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure BGMH received grants from Merck Sharp & Dohme during the conduct of the study; was an advisory board member for Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Pfizer, Eisai, Takeda, and AstraZeneca; and received grants from Amgen outside the submitted work. EM-C serves on the advisory board of Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, and Sanofi outside the submitted work and received grant from Merck Sharp & Dohme during the conduct of the study. LM received research grant from Merck Sharp & Dohme during the conduct of the study. ÅB received grant from Merck Sharp & Dohme during the conduct of the study and grants from Merck Sharp & Dome, Bristol Myers Squibb, and Sanofi outside the submitted work. RG received grants from Merck Sharp & Dohme during the conduct of the study; personal fees and non-financial support from Bristol Myers Squibb, Roche Pharma, Merck Serono, Pierre Fabre, Sanofi Regeneron, and Almirall Hermal; grants, personal fees, and non-financial support from Amgen and Novartis; personal fees from Merck Sharp & Dohme, Bayer, Immunocore, Sun Pharma, and 4SC; grants and personal fees from Pfizer; and grants from Johnson & Johnson outside the submitted work. OR, RGM, JS, FG, and AJ received research grant from Merck Sharp & Dohme during the conduct of the study. AA received grants from Merck Sharp & Dohme during the conduct of the study; grants, personal fees, and other from Merck Sharp & Dohme, BMS, Novartis, Roche, and Pierre Fabre; and personal fees from Sanofi and Amgen outside the submitted work. NM received grants from Merck Sharp & Dohme during the conduct of the study; grants and personal fees from BMS and Merck Sharp & Dohme; and personal fees from Novartis, Roche, Pierre Fabre, Sun Pharma, AbbVie, and Sanofi outside the submitted work. SB received grants from Merck Sharp & Dohme during the conduct of the study and personal fees from Merck Sharp & Dohme, BMS, and Merck KGaA outside the submitted work. PZ, BG, and RFS are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, who owns stock in Merck & Co., Inc., Kenilworth, NJ, USA. J-JG received grants from Merck Sharp & Dohme during the conduct of the study and personal fees from Merck Sharp & Dohme, BMS, Novartis, Roche, Sanofi, Pierre Fabre, Merck KGaA, Pfizer, and Sun Pharma outside the submitted work. Data sharing Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD) is committed to providing qualified scientific researchers access to anonymized data and clinical study reports from the company's clinical trials for the purpose of conducting legitimate scientific research. MSD is also obligated to protect the rights and privacy of trial participants and, as such, has a procedure in place for evaluating and fulfilling requests for sharing company clinical trial data with qualified external scientific researchers. The MSD data-sharing website (available at http://engagezone.msd.com/ds_documentation.php) outlines the process and requirements for submitting a data request. Applications will be promptly assessed for completeness and policy compliance. Feasible requests will be reviewed by a committee of MSD subject matter experts to assess the scientific validity of the request and the qualifications of the requestors. In line with data privacy legislation, submitters of approved requests must enter into a standard data-sharing agreement with MSD before data access is granted. Data will be made available for request after product approval in the US and EU or after product development is discontinued. There are circumstances that may prevent MSD from sharing requested data, including country- or region-specific regulations. If the request is declined, it will be communicated to the investigator. Access to genetic or exploratory biomarker data requires a detailed, hypothesis-driven statistical analysis plan that is collaboratively developed by the requestor and MSD subject matter experts; after approval of the statistical analysis plan and execution of a data-sharing agreement, MSD will either perform the proposed analyses and share the results with the requestor or will construct biomarker covariates and add them to a file with clinical data that is uploaded to an analysis portal so that the requestor can perform the proposed analyses.