Primary analysis of Phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma who progressed on or were intolerant to hedgehog inhibitors
Karl D. Lewis1; K. Peris2; A. Sekulic3; A.J. Stratigos4; L. Dunn5; Z. Eroglu6; A.L.S. Chang7; M.R. Migden8; S.Y. Yoo9; K. Mohan9; E. Coates9; E. Okoye9; J.F. Baurain10; O. Bechter11; A. Hauschild12; M.O. Butler13; L. Hernández-Aya14; L. Licitra15; R.I. Neves16; E.S. Ruiz17; F. Seebach9; I. Lowy9; P. Goncalves9; M.G. Fury9
1. Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA; 2. Dermatology, Department of Medical and Surgical Sciences, Catholic University of the Sacred Heart, Rome, Italy and Fondazione Policlinico Universitario A Gemelli-IRCCS, Rome, Italy; 3. Department of Dermatology, Arizona Mayo Clinic, Scottsdale, AZ, USA; 4. First Department of Dermatology-Venereology, Andreas Sygros Hospital-University of Athens, Athens, Greece; 5. Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 6. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA; 7. Dermatology Department, Stanford University School of Medicine, Redwood City, CA, USA; 8. Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 9. Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 10. Department of Medical Oncology, Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium; 11. Department of General Medical Oncology, University Hospitals, Leuven, Belgium; 12. Department of Dermatology, Schleswig-Holstein University Hospital, Kiel, Germany; 13. Division of Medical Oncology and Hematology, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; 14. Department of Internal Medicine, University of Miami, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA; 15. Department of Medical Oncology Head and Neck Cancer, Istituto Nazionale dei Tumori, Milan, Italy and Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; 16. Department of Cutaneous Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 17. Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Introduction & Objectives
Cemiplimab is the first treatment approved in the US (as cemiplimab-rwlc) for patients with metastatic basal cell carcinoma (mBCC) or locally advanced disease (laBCC) after hedgehog inhibitor (HHI) treatment or for whom an HHI is not appropriate. Cemiplimab provided substantial clinical benefit and an acceptable safety profile in patients with laBCC who discontinued HHI therapy due to progressive disease (PD), intolerance, or no better than stable disease (SD) after 9 months (NCT03132636). Here, we present the primary analysis of the mBCC cohort.
Materials & Methods
Patients with mBCC (nodal or distant) post-HHI treatment received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until PD. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Key secondary endpoints included safety and tolerability, ORR per investigator (INV) assessment,
duration of response (DOR), progression-free survival (PFS), overall survival (OS), and complete response (CR) rate (data cutoff date: May 20, 2021).
Results
Fifty-four patients were enrolled (70.4% male; median age 63.5 years [range, 38–90]; Eastern Cooperative Oncology Group performance status 0 [66.7%] and 1 [33.3%]). Median duration of follow-up was 8.4 months (range 1.5–36.2). ORR per ICR was 24.1% (95% confidence interval [CI], 13.5–37.6); with 1 CR and 12 partial responses (PRs). ORR per INV was 25.9% (95% CI, 15.0–39.7), with 2 CRs and 12 PRs. Among responders, median time to response per ICR was 4.0 months (range, 2.0–10.5). Estimated median DOR per ICR was 16.7 months (95% CI, 9.8 not evaluable). Disease control rate was 63.0% (95% CI, 48.7–75.7) per ICR and 70.4% (95% CI, 56.4–82.0) per INV. Median OS was not reached. Median PFS per ICR was 8.3 months (95% CI, 4.2–15.9). The most common treatment-related adverse events were fatigue (37.0%), diarrhea (14.8%), pruritus (13.0%), hyperthyroidism (9.3%), and arthralgia (9.3%) as well as hypothyroidism, asthenia, constipation, and maculo-papular rash (7.4% each). There
were no treatment-related deaths.
Conclusions
Cemiplimab provided clinically meaningful antitumor activity, including durable responses, and an acceptable safety profile in patients with mBCC who had progressed on or were intolerant to HHI therapy.