1091P - Neoadjuvant cemiplimab for stage II–IV cutaneous squamous cell carcinoma (CSCC): 2-year follow-up and biomarker analyses

Background

Neoadjuvant (neoadj) cemiplimab (cemi) led to high pathologic complete response (pCR) and major pathologic response (MPR) rates in advanced, resectable CSCC. We present 2-year event-free, disease-free and overall survival (EFS, DFS, OS), and new biomarker analyses.

Methods

This non-randomised multicentre phase 2 study (NCT04154943) included 79 patients (pts) with stage II–IV (M0) CSCC treated with ≤4 doses of neoadj cemi followed by curative-intent surgery. Adjuvant cemi, radiotherapy (RT) or observation alone were per investigator discretion. EFS, DFS and OS were estimated using the Kaplan-Meier method. Tumour tissue collected pretreatment and at day (D) 22 ± 3 (after the first cycle of cemi) was analyzed via flow cytometry and bulk RNA/TCR sequencing.

Results

As of 1 Dec 2023, median follow-up was 29.4 months (range: 1.3–41.4) for all 79 pts. Among 70 pts who underwent surgery, adjuvant care was observation alone (n=32), RT (n=17), cemi (n=16), or not available (n=5). 0/40 and 1/10 pts with pCR and MPR, respectively, experienced recurrence. 24-month EFS was 86% (95% CI: 75–92) for all pts: 92% (78–97) for pts with pCR; 89% (43-98) for pts with MPR; 64% (35-83) for non-responders/not evaluable. DFS was 90% (80–96) for pts who underwent surgery. OS was 86% (76–92) for all pts. For pts who received adjuvant cemi (n=16), 25% had ≥1 grade 3 or 4 treatment-emergent adverse event (TEAE); no additional serious TEAEs were observed since the last report. Neoadj cemi increased the % of Ki67+ PD1+ CD8 and CD4 T cells in circulation at D22 (n=69; paired t-test p<0.001). Bulk RNA sequencing from paired tumours collected at baseline and D22 (n=25) demonstrated increased expression of effector T-cell-related genes and significant enrichment of T cell activation, interferon-γ/α response, and TCR signalling pathways. Pts with pCR appeared to have significantly increased clonal abundance at D22 vs pts not experiencing pCR (Gini coefficient; paired Wilcoxon p=0.01).

Conclusions

In resectable stage II–IV CSCC, neoadj cemiplimab demonstrates favourable oncologic outcomes with 2 years of follow-up. Results from biomarker analyses indicate that neoadj cemiplimab enhances T cell responses, with increased clonal abundance in responders.

Clinical trial identification

NCT04154943.

Editorial acknowledgement

Writing assistance was provided by Brian Head, PhD, of Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Alpha, a division 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

D. Rischin: Financial Interests, Personal, Research Funding: Regeneron Pharmaceuticals, Inc, ALX Oncology, Merck Sharp & Dohme, Roche, AstraZeneca, Decibel Therapeutics, Sanofi; Financial Interests, Personal, Advisory Board: Eisai, Bicara, GSK, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc, Sanofi. D.M. Miller: Financial Interests, Personal, Speaker, Consultant, Advisor: 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, Personal, Research Funding: Kartos Therapeutics, NeoImmune Tech, Inc, Regeneron Pharmaceuticals, Inc. N.I. Khushalani: Financial Interests, Personal, Other, Grants and advisory board fees: Regeneron Pharmaceuticals, Inc, Bristol Myers Squibb, Merck, Novartis; Financial Interests, Personal, Advisory Board: Iovance, Instil Bio, Castle Biosciences, Nektar, Immunocore, Incyte (data safety monitoring committee), AstraZeneca (data safety monitoring committee), Replimune; Financial Interests, Personal, Research Grant: Replimune, GSK, HUYA, Celgene, Ideaya Biosciences, Modulation Therapeutics; Financial Interests, Personal, Other, Honoraria: Nektar (study steering committee); Financial Interests, Personal, Other, Travel support: Regeneron Pharmaceuticals, Inc, Castle Biosciences; 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, Officer, Advisory board and consulting fees: Genentech; Financial Interests, Personal, Other, Advisory board and consulting fees: Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Sanofi; Financial Interests, Personal, Member of Board of Directors: Checkpoint Therapeutics. E.J. Lipson: Financial Interests, Personal, Other, Advisory board and consulting fees: Bristol Myers Squibb, Eisai, Genentech, Instill Bio, Merck, Natera, Nektar Therapeutics, Odonate Therapeutics, Pfizer, Rain Therapeutics, Regeneron Pharmaceuticals, Inc, Sanofi; Financial Interests, Personal, Speaker, Consultant, Advisor: Macrogenics, OncoSec, Genentech, Merck, Natera, Novartis, Odonate Therapeutics, Regeneron Pharmaceuticals, Inc, Sanofi. F. Meier: Financial Interests, Personal, Advisory Board, Travel support, speaker’s fees or advisor’s honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Research Funding: Novartis, Roche. P.L. Swiecicki: Financial Interests, Institutional, Research Grant: Ascentage Pharma, Pfizer; Financial Interests, Institutional, Advisory Board: Elevar Therapeutics, Prelude Therapeutics, Regeneron Pharmaceuticals, Inc. J. Atlas: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Castle Biosciences, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi. J.L. Geiger: Financial Interests, Institutional, Research Funding: Alkermes, EMD Serono, Merck, Regeneron Pharmaceuticals, Inc, Roche/Genentech; Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas, Exelixis, Merck, Regeneron Pharmaceuticals, Inc. A. Hauschild: Financial Interests, Personal and Institutional, Other, Institutional grants, speaker’s honoraria and consultancy fees: Amgen, Bristol Myers Squibb, Novartis, Pierre Fabre, Roche; Financial Interests, Personal and Institutional, Other, Institutional grants and consultancy fees: Philogen, Regeneron Pharmaceuticals, Inc; Financial Interests, Personal and Institutional, Other, Institutional grants and personal fees: Eisai, Sanofi/Genzyme, Replimune, NeraCare, MSD/Merck; Financial Interests, Personal and Institutional, Other, Institutional grans and personal fees: Merck/Pfizer; Financial Interests, Personal, Other, Personal fees: Dermagnostix, Highlight Therapeutics, Immunocore, Incyte, IO Biotech, Iovance, Kyowa Kirin, Seagen; Financial Interests, Institutional, Other, Institutional grants: Huya Biosciences. J.H. Choe: Financial Interests, Personal, Speaker, Consultant, Advisor: Exelixis, Eisai, Coherus Biosciences, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc; Financial Interests, Institutional, Research Funding: Genmab A/S, Roche/Genentech, ALX Oncology, Merck Sharp & Dohme, Coherus Biosciences. B.G.M. Hughes: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer, Roche; Financial Interests, Institutional, Research Funding: Amgen. S. Yoo, L. Brennan, 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. N. Gross: Financial Interests, Institutional, Research Funding: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Advisory Board: PDS Biotechnology, GeoVax, Sanofi-Genzyme, Merck. All other authors have declared no conflicts of interest.