Neoadjuvant cemiplimab in patients (pts) with stage II–IV (M0) cutaneous squamous cell carcinoma (CSCC): Primary analysis of a phase II study

ABSTRACT

Background: CSCC is highly immune-responsive;a prior pilot study demonstrated a high rate of pathologic complete response (pCR) or major pathologic response (MPR, ≤10% viable tumor), using cemiplimab anti-programmed death 1 (PD-1) therapy in the neoadjuvant setting. Here, we present the primary analysis of a confirmatory, open-label, multicenter, Phase 2, single-arm trial of neoadjuvant cemiplimab in pts with resectable Stage II–IV (M0) CSCC. Methods: Pts received cemiplimab 350 mg IV q3W for up to 4 doses before surgery. The primary endpoint was pCR rate per independent central pathologic review (ICPR). Key secondary endpoints included MPR rate per ICPR, objective response rate (ORR;complete response [CR] + partial response [PR]) per RECIST v1.1, investigator-assessed pCR and MPR, safety and tolerability. Results: At data cutoff date of 01 Dec 2021, 79 pts were enrolled (67 male;median age 73.0 yrs [range, 66.0–81.0];ECOG performance status 0 (n=60) and 1 (n=19) with stage II (n=5), III (n=38), or IV(M0) (n =36) disease;62 pts received all 4 doses (median number of doses given (Q1Q3), 4 (44);70 pts underwent surgery. The study met its primary endpoint pCR was observed in 40 (50.6%) pts (95% confidence interval [CI], 39.1–62.1%). MPR was observed in an additional 10 (12.7%) pts (95% CI, 6.2–22.0%). ORR was 68.4% (95% CI, 56.9–78.4) (5 CR, 49 PR, 16 stable disease, 8 progressive disease (PD), 1 non evaluable. Reasons 9 pts did not have surgery 3 responders declined surgery, 2 lost to follow-up or noncompliance, 2 had inoperable PD, 2 due to AE. Fourteen (17.7%) pts experienced Grade ≥3 AE. Four pts died due to AEs 1 exacerbation of cardiac failure, 2 myocardial infarctions, and 1 COVID-19 pneumonia. The most common AEs regardless of attribution (all grades) were fatigue (30.4%), rash maculo-papular (13.9%), diarrhea (13.9%) and nausea (13.9%). Conclusions: The pCR + MPR of 63.3% by ICPR in pts with Stage II–IV (M0) CSCC is the highest observed in a multicenter anti-PD-1 neoadjuvant monotherapy study for any solid tumor type. The safety profile of neoadjuvant cemiplimab is consistent with previous anti-PD-1 monotherapy experience. Ongoing follow-up will describe disease-free survival. Clinical trial identification NCT04154943. Editorial acknowledgement Medical writing support was provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Legal entity responsible for the study Regeneron Pharmaceuticals, Inc., and Sanofi. Funding: Regeneron Pharmaceuticals, Inc., and Sanofi. Disclosure N. Gross Financial Interests, Personal, Research Grant Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Board PDS Biotechnology, Shattuck Labs and Genzyme;Financial Interests, Personal, Advisory Role PDS Biotechnology, Shattuck Labs and Genzyme. D.M. Miller Financial Interests, Personal, Advisory Role Castle Biosciences, EMD Serono, Merck KGaA, Merck Sharpe & Dome, Pfizer, Regeneron, Sanofi Genzyme;Financial Interests, Personal, Ownership Interest Checkpoint Therapeutics;Financial Interests, Personal, Research Grant Kartos Therapeutics, NeoImmune Tech, Inc., Regeneron Pharmaceuticals, Inc. N. Khushanlani Financial Interests, Personal, Research Grant Regeneron Pharmaceuticals, Inc., Bristol Myers Squibb, HUYA Bioscience International, Merck, Novartis, GlaxoSmithKline, Celgene, Amgen;Financial Interests, Personal, Advisory Board EMD Serono, Regeneron Pharmaceuticals, Inc., Genentech, AstraZeneca (data safety monitoring committee), Merck, Array Biopharma, Jounce Therapeutics, Immunocore, Bristol Myers Squibb, HUYA Bioscience International;Financial Interests, Personal, Other, honoraria Sanofi;Financial Interests, Personal, Stocks/Shares Bellicum Pharmaceuticals, Mazor Robotics, Amarin, Transenetrix. V. Divi Financial Interests, Institutional, Research Grant Genentech. E.S. Ruiz Financial Interests, Personal, Advisory Board Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Int rests, Personal, Advisory Role, consulting fees Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Interests, Personal, Member of the Board of Directors Checkpoint Therapeutics. E.J. Lipson Financial Interests, Personal, Other, Advisory board and consulting fees Bristol Myers-Squibb, Eisai, Genentech, Immunocore, Instil Bio, MacroGenics, Merck, Natera, Nektar Therapeutics, Odonate Therapeutics, OncoSec, Pfizer, Rain Therapeutics, Regeneron, Sanofi;Financial Interests, Institutional, Research Grant Bristol Myers Squibb, Merck, Regeneron. 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 and Sanofi;Financial Interests, Personal, Research Grant Novartis and Roche. P.L. Swiecicki Financial Interests, Institutional, Research Grant Ascentage Pharma, Pfizer;Financial Interests, Personal, Advisory Board Prelude Therapeutics, Elevar Therapeutics, Regeneron Pharmaceuticals. J.L. Atlas Financial Interests, Personal, Advisory Role Regeneron Pharmaceuticals, Inc., Sanofi, and Bristol Myers Squibb. J.L. Geiger Financial Interests, Institutional, Research Grant Alkermes, Debio, Merck, Regeneron Pharmaceuticals, Inc., and Roche/Genentech;Financial Interests, Personal, Advisory Role Exelixis, Merck and Regeneron Pharmaceuticals, Inc. A. Hauschild Financial Interests, Personal and Institutional, Other, Institutional grants, speaker’s honoraria and consultancy fees Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Provectus and Roche;Financial Interests, Institutional, Other, Institutional grants and consultancy fees EMD Serono, Philogen and Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Role OncoSec Medical. J.H. Choe Financial Interests, Personal, Advisory Role Exelixis, Coherus Biosciences, Regeneron Pharmaceuticals, Inc. B.G.M. Hughes Financial Interests, Personal, Advisory Role AstraZeneca, Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer and Roche;Financial Interests, Institutional, Research Grant Amgen. S. Yoo Financial Interests, Personal, Full or part-time Employment Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares Regeneron Pharmaceuticals, Inc. K. Fenech Financial Interests, Personal, Full or part-time Employment Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares Regeneron Pharmaceuticals, Inc. M.D. Mathias Financial Interests, Personal, Full or part-time Employment Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares Regeneron Pharmaceuticals, Inc. H. Han Financial Interests, Personal, Full or part-time Employment Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares Regeneron Pharmaceuticals, Inc. 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, GlaxoSmithKline, ALX Oncology;Financial Interests, Personal, Advisory Role Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb;Financial Interests, Personal, Advisory Board Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb. All other authors have declared no conflicts of interest.