1066P - Extended-dose cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC): Primary analysis of phase II results

Background

Cemiplimab 350 mg every 3 weeks (Q3W) intravenously (IV) is a standard of care for advanced CSCC. For some patients and physicians, extended dosing may allow flexibility in treatment management. Here, we present the primary analysis of data from cemiplimab 600 mg every 4 weeks (Q4W) IV in advanced CSCC. Pharmacokinetics (PK) modelling indicated that this dosing regimen would maintain cemiplimab C_trough at the level of the approved Q3W regimen.

Methods

Patients received cemiplimab 600 mg Q4W IV for up to 48 weeks and tumour assessments every 8 weeks. The primary endpoint was ORR by independent central review (ICR) per RECIST 1.1 and/or modified WHO criteria. Key secondary endpoints included duration of response (DOR), complete response (CR) rate and the PK and safety profiles of cemiplimab. Data cut-off was 18 April 2020.

Results

Sixty-three patients were enrolled (mCSCC, n=39; laCSCC, n=24; median age, 74 years; male, 84%; 14% had received prior systemic therapy). With median follow-up of 9.2 months (range: 1.0–16.5), ORR by ICR was 58.7% (95% CI: 45.6–71.0) with a CR rate of 17.5%. Median DOR had not been reached; Kaplan–Meier estimation of ongoing response at 12 months was 89.4% (95% CI: 70.0–96.6). Durable disease control rate was 76.2% (95% CI: 63.8–86.0). Median progression-free survival per ICR and overall survival had not been reached. Extended-dose cemiplimab resulted in observed mean (SD) C_max of 281 (235) mg/L and C_trough of 62.5 (24.1) mg/L. The most common treatment-emergent adverse events (AEs) were diarrhoea, pruritis (each n=15; 23.8%) and fatigue (n=14; 22.2%). Investigator-assessed Grade ≥3 immune-mediated AEs occurred in eight (12.7%) patients.

Conclusions

Significant efficacy of cemiplimab 600 mg Q4W IV (ORR 58.7%, CR 17.5% per ICR) was demonstrated, in line with that of the approved Q3W regimen. No new safety signals are observed, and the PK data confirm maintenance of C_trough levels seen with the 350mg Q3W IV regimen.

Clinical trial identification

NCT02760498.

Editorial acknowledgement

Medical writing support was provided by Nila Bhana, MSc, 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, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Roche, Merck Sharp & Dohme, Bristol-Myers Squibb and GlaxoSmithKline; Non-Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline and Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel and accommodation: Merck Sharp & Dohme and GlaxoSmithKline. B.G.M. Hughes: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Pfizer, Roche, Eisai and Merck; Financial Interests, Institutional, Research Grant: Amgen. D. Schadendorf: Financial Interests, Institutional, Other, Institutional patients’ fees : Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Advisory Board: Amgen and Leo Pharma; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Roche, Novartis, Bristol-Myers Squibb and Merck-EMD; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Bristol-Myers Squibb and Merck-EMD; Financial Interests, Personal, Other, Patients’ fees : Roche, Novartis, Bristol-Myers Squibb and Merck-EMD; Financial Interests, Personal, Advisory Board: Incyte and Pierre Fabre; Financial Interests, Personal, Invited Speaker: Incyte and Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD and Philogen; Financial Interests, Personal, Other, Patients’ fees : MSD and Philogen; Financial Interests, Personal, Other, Steering committee honorarium fees: 4SC; Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer and Array. S. Bowyer: Financial Interests, Personal, Advisory Board: Sanofi ; Financial Interests, Personal, Sponsor/Funding, Virtual meeting sponsorship : Bristol Myers Squibb and MSD Australia. S. Trabelsi: Financial Interests, Personal, Invited Speaker: Novartis, AbbVie, Bristol Myers Squibb, Sun Pharma and Pierre Fabre; Financial Interests, Personal, Advisory Board: Novartis, AbbVie, Bristol Myers Squibb, Sun Pharma and Pierre Fabre. F. Meier: Financial Interests, Personal, Invited Speaker: Novartis, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre and Sanofi; Financial Interests, Personal, Advisory Role: Novartis, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Pierre Fabre and Sanofi; Financial Interests, Personal, Other, Travel support : Novartis, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre and Sanofi; Financial Interests, Personal, Research Grant: Novartis and Roche. T. Eigentler: Financial Interests, Personal, Advisory Role: Sanofi-Genzyme, Bristol Myers Squibb, Roche, Novartis and Merck Sharp & Dohme; Financial Interests, Personal, Other, Consulting roles: Sanofi-Genzyme, Bristol Myers Squibb, Roche, Novartis and Merck Sharp & Dohme; Financial Interests, Personal, Speaker’s Bureau: Roche and Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Novartis and Bristol-Myers Squibb. M.R. Migden: Financial Interests, Personal, Other, Honoraria : Regeneron Pharmaceuticals, Inc., Sanofi, Novartis, Genentech, Eli Lilly and Sun Pharma; Financial Interests, Personal, Other, Travel expenses: Regeneron Pharmaceuticals, Inc., Sanofi, Novartis, Genentech, Eli Lilly and Sun Pharma; Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Novartis, Genentech and Eli Lilly. A. Hauschild: Financial Interests, Institutional, Research Grant: Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme/Merck, Pierre Fabre, Provectus, Roche and Novartis; Financial Interests, Personal, Invited Speaker: Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme/Merck, Pierre Fabre, Provectus, Roche and Novartis; Financial Interests, Personal, Other, Consultancy fees : Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme/Merck, Pierre Fabre, Provectus, Roche and Novartis; Financial Interests, Institutional, Research Grant: Merck Serono, Philogen and Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Consultancy fees : Merck Serono, Philogen and Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Consultancy fees : OncoSec. C.D. Schmults: Financial Interests, Personal, Other, Steering committee member : Castle Biosciences; Financial Interests, Personal, Other, Steering committee member and consultant : Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Consultant: Sanofi; Financial Interests, Personal, Research Grant: Castle Biosciences, Regeneron Pharmaceuticals, Inc., Novartis, Genentech and Merck; Financial Interests, Personal, Leadership Role, Chair for the National Comprehensive Cancer Network: National Comprehensive Cancer Network. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.. A. Paccaly: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.. V. Jankovic: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.. F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.. S. Drutman: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.. J. Booth: 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.; Financial Interests, Personal, Other, Has patents pending : Regeneron Pharmaceuticals, Inc.. A. Guminski: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb and Sun Pharma; Non-Financial Interests, Personal, Other, Travel support: Bristol-Myers Squibb, Sun Pharma and Astellas; Financial Interests, Personal, Advisory Board: Merck KGaA, Eisai and Pfizer; Financial Interests, Personal, Other, Clinical trial unit support : PPD Australia. All other authors have declared no conflicts of interest.