Poster Presentation Joint Scientific Meeting of the Australian & NZ Head & Neck Cancer Society & NZ Association of Plastic Surgeons

Primary analysis of Phase 2 results for cemiplimab in patients (pts) with locally advanced basal cell carcinoma (laBCC) who progress on or are intolerant to hedgehog inhibitors (HHIs) (1355)

Alexander J. Stratigos 1 , Aleksandar Sekulic 2 , Ketty Peris 3 , Oliver Bechter 4 , Caroline Dutriaux 5 , Martin Kaatz 6 , Karl D. Lewis 7 , Nicole Basset-Seguin 8 , Anne Lynn S. Chang 9 , Stéphane Dalle 10 , Almudena Fernandez Orland 11 , Lisa Licitra 12 , Caroline Robert 13 , Claas Ulrich 14 , Axel Hauschild 15 , Michael R. Migden 16 , Reinhard Dummer 17 , Siyu Li 18 , Timothy Bowler 18 , Matthew G. Fury 18
  1. Department of Dermatology-Venereology, Andreas Sygros Hospital-National and Kapodistrian University of Athens, Athens, Greece
  2. Department of Dermatology, Arizona Mayo Clinic , Arizona, AZ, USA
  3. Institute of Dermatology, Catholic University of the Sacred Heart and Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy
  4. Department of General Medical Oncology, University Hospitals, Leuven, Belgium
  5. Department of Dermatology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
  6. Department of Dermatology, SRH Wald-Klinikum Gera GmbH, Gera, Germany
  7. Division of Medical Oncology, University of Colorado Hospital, Aurora, CO, USA
  8. Department of Dermatology, Hôpital Saint-Louis, Paris, France
  9. Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
  10. Department of Dermatology, Centre Hospitalier Lyon-Sud, Lyon, France
  11. Department of Dermatology, Hospital Universitario Virgen Macarena , Seville, Spain
  12. Medical Oncology Head and Neck Cancer Department, Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
  13. Dermatology Unit, Gustave Roussy Cancer Center and Paris-Saclay University, Villejuif, France
  14. Skin Cancer Centre, Charite-Universitiitsmedizin Berlin, Berlin, Germany
  15. Department of Dermatology, University of Kiel , Kiel, Germany
  16. Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA
  17. Department of Dermatology, University Hospital Zurich , Zurich, Switzerland
  18. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA

Purpose: There is no approved therapeutic option post-HHI for pts with laBCC. Cemiplimab, an antibody, is approved for treatment of advanced cutaneous squamous cell carcinoma (CSCC) in pts who are not candidates for curative surgery/radiation. Both BCC and CSCC are keratinocytic tumours with high tumour mutational burden (TMB) from ultraviolet mutagenesis and are potentially amenable to immunotherapy. We present the primary analysis of the laBCC cohort from the pivotal Phase 2 study of cemiplimab in the second-line (or greater) setting.

Methodology: Pts with laBCC received cemiplimab 350 mg Q3W IV (≤93 weeks or until progression). The primary endpoint was objective response rate (ORR) by independent central review (ICR). Secondary objectives included safety and tolerability, duration of response (DOR), progression-free survival (PFS) and overall survival (OS). ORR included two responses confirmed after the data cut-off date of 17 February 2020.

Results: 84 pts were enrolled; 66.7% male; median age (range): 70 years (42−89); median follow-up: 15 months (range: 0.5−25). ORR per ICR was 31% (95% CI: 21−42), including five complete responses and 21 partial responses. Median DOR and median PFS/OS have not been reached. Per Kaplan–Meier, an estimated 85% of responses were ongoing at 12 months. Estimated PFS for all patients was 19 months. The most common adverse events (AEs) were fatigue (30%), diarrhoea (24%) and pruritus (21%); 17% of patients discontinued treatment due to AEs. Median baseline TMB was 58.2 and 23.5 mutations/Mb among responding (n=18) and non-responding (n=38) pts, respectively, but responses occurred at all TMB levels. Exploratory biomarker analysis identified downregulation of major histocompatibility complex-I expression as a potential immune evasion mechanism in non-responding BCCs with high TMB.

Conclusion: Cemiplimab is the first agent to establish clinical benefit for pts with laBCC who progress on or are intolerant to HHI therapy, regardless of biomarker status.

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