1088MO - A phase II study of neoadjuvant cemiplimab for stage II to IV cutaneous squamous cell carcinoma (CSCC): One-year follow-up

Background

We previously reported a high rate of pathologic complete response (pCR) or major pathologic response (MPR) to neoadjuvant (neoadj) cemiplimab (anti-programmed cell death-1) among 79 patients (pts) with locoregionally advanced, resectable CSCC. Here, we present 1-year follow-up data, with event-free, disease-free and overall survival (EFS, DFS, OS; NCT04154943).

Methods

This non-randomised multicentre phase II study had 2 parts. In part 1, pts with resectable stage II–IV (M0) CSCC received neoadj cemiplimab 350 mg every 3 weeks (Q3W) for up to 4 doses followed by curative-intent surgery. In Part 2, per investigator discretion, pts received adjuvant cemiplimab for up to 48 weeks or radiotherapy (RT) or observation only. EFS (time from first dose of neoadj cemiplimab to progressive disease precluding surgery, inability to undergo complete resection, disease recurrence, or death due to any cause); DFS (time from surgery until CSCC recurrence or death due to any cause) and OS were summarised by the Kaplan-Meier method.

Results

At December 1, 2022 data cut-off, median duration of follow-up was 18.7 months (range: 1.3–30.4) for all 79 pts. Among 70 pts who had surgery, the most common choices for subsequent care were observation only (n=29), cemiplimab (n=16), or RT (n=12) or other (Table). None of 40 pts with pCR and 1 of 10 pts with MPR experienced recurrence. Estimated 12-month EFS was 89% (95% confidence interval [CI]: 79–94%) for all pts and 95% (95% CI: 81–99%) for pts with pCR. Of 70 pts who completed surgery, 12-month DFS was 92% (95% CI: 82–97%). For all 79 pts: estimated 12-month OS rate was 92% (95% CI: 83–96%). Of 16 pts who received cemiplimab in part 2, there were 2 serious adverse events: grade 3 cardiomyopathy and grade 3 hypophysitis. Table: 1088MO

^aPatients in the “observation only” group had 4 doses of cemiplimab in Part 1. ^bPatients in the “imaging only” group had <4 doses of cemiplimab due to progressive disease in Part 1. ^cIncluded: lost to follow up (n=2), withdrawal of consent (n=1), fatal post-op COVID pneumonia (n=1), post-op death prior to starting Part 2 (n=1).

Conclusions

In pts with resectable stage II–IV CSCC, neoadj cemiplimab demonstrated favourable EFS, DFS and OS rates, and no recurrences in pts with pCR at a median follow-up of 18.7 months. There were no new safety signals with cemiplimab.

Clinical trial identification

NCT04154943.

Editorial acknowledgement

Medical writing support was provided by Jenna Lee, MSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., Sanofi.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc., and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc., and Sanofi.

Disclosure

N. Gross: Financial Interests, Institutional, Funding: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Advisory Board: PDS Biotechnology, Shattuck Labs, DragonFly Therapeutics, Sanofi, Merck, Genzyme; Financial Interests, Personal, Advisory Role: PDS Biotechnology, Shattuck Labs, DragonFly Therapeutics, Sanofi, Merck, Genzyme. D.M. Miller: Financial Interests, Personal, Advisory Role: Castle Biosciences, EMD Serono, Merck KGaA, Merck Sharpe & Dohme, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme; Financial Interests, Personal, Stocks/Shares: Checkpoint Therapeutics, Avstera Therapeutics Corp; Financial Interests, Institutional, Funding: Kartos Therapeutics, NeoImmune Tech, Inc., Regeneron Pharmaceuticals, Inc. N.I. Khushalani: Financial Interests, Personal, Advisory Board: Regeneron Pharmaceuticals, Inc., Bristol Myers Squibb, Merck, Novartis, Iovance, Instil Bio, Castle Biosciences, Nektar, Incyte (data safety monitoring committee), AstraZeneca (data safety monitoring committee), Jounce Therapeutics; Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc., Bristol Myers Squibb, Merck, Novartis, Replimune, GSK, HUYA, Celgene; Financial Interests, Personal, Other, Honoraria: Genzyme, NCCN (from Pfizer), Nektar (study steering committee); Financial Interests, Personal, Stocks or ownership: Bellicum Pharmaceuticals, Amarin, Transenetrix. V. Divi: Financial Interests, Institutional, Research Funding: Genentech; Financial Interests, Personal, Advisory Board: Regeneron Pharmaceuticals, Inc. E. Ruiz: Financial Interests, Personal, Advisory Board: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi; Financial Interests, Personal, Advisory Role: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi; Financial Interests, Personal, Member of Board of Directors: Checkpoint Therapeutics. E.J. Lipson: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Sanofi, Regeneron, Genentech, Eisai, Instil Bio, Natera, Nektar Therapeutics, Pfizer, Rain Therapeutics, CareDx, Immunocore, Novartis, Replimune, HUYA Bioscience International; Financial Interests, Personal, Other, Consultant: OncoSec; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Regeneron, Merck, Sanofi. F. Meier: Financial Interests, Personal, Other, Travel support, speaker’s fees or advisor’s honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Institutional, Research Funding: Novartis, Roche. P.L. Swiecicki: Financial Interests, Institutional, Research Grant: Ascentage Pharma, Pfizer; Financial Interests, Personal, Advisory Board: Elevar Therapeutics, Prelude Therapeutics, Regeneron Pharmaceuticals, Inc. J.L. Atlas: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Castle Biosciences, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Castle Biosciences, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi. J.L. Geiger: Financial Interests, Institutional, Research Funding: Alkermes, Merck, Regeneron Pharmaceuticals, Inc., Roche/Genentech; Financial Interests, Institutional, Sponsor/Funding: EMD Serono; Financial Interests, Personal, Advisory Board: Astellas, Exelixis, Merck, Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Advisory Role: Astellas, Exelixis, Merck, Regeneron Pharmaceuticals, Inc. A. Hauschild: Financial Interests, Personal, Advisory Board: BMS, MSD, Philogen, Pierre Fabre, Regeneron, Roche, Sanofi, Novartis, Eisai, Immunocore, Replimune, Seagen, Dermagnostix, Neracare, IO Biotech, Incyte, Highlight Therapeutics, Agenus; Financial Interests, Personal, Invited Speaker: Merck, Pfizer; Financial Interests, Institutional, Local PI: BMS, MSD, Pierre Fabre, Amgen, Roche, Agenus; Financial Interests, Institutional, Coordinating PI: Regeneron, Novartis. J.H. Choe: Financial Interests, Personal, Advisory Role: Exelixis, Coherus Biosciences, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc.; Financial Interests, Institutional, Research Funding: Genmab A/S, Arcus Biosciences. B.G.M. Hughes: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer, Roche; Financial Interests, Institutional, Research Funding: Amgen. S. Yoo, M.D. Mathias, H. Han, M.G. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. D. Rischin: Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Genentech, Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Merck KGaA, Bristol Myers Squibb, GSK, ALX Oncology; Non-Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GSK, Bristol Myers Squibb; Non-Financial Interests, Personal, Steering Committee Member: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GSK, Bristol Myers Squibb. All other authors have declared no conflicts of interest.