Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors

• DOI: 10.1016/j.annonc.2023.10.123
• Publication Date: 2023-12-09T23:03:53Z
• Authors: K.D. Lewis; K. Peris; A. Sekulic; A.J. Stratigos; L. Dunn; Z. Eroglu; A.L.S. Chang; M.R. Migden; S.-Y. Yoo; K. Mohan; E. Coates; E. Okoye; T. Bowler; J.-F. Baurain; O. Bechter; A. Hauschild; M.O. Butler; L. Hernandez-Aya; L. Licitra; R.I. Neves; E.S. Ruiz; F. Seebach; I. Lowy; P. Goncalves; M.G. Fury
• Keywords: Adult; Male; Skin Neoplasms; metastatic basal cell carcinoma; Antineoplastic Agents; Middle Aged; Ligands; Antibodies, Monoclonal, Humanized; Amides; Carcinoma, Basal Cell; PD-1; Disease Progression; Humans; Female; Hedgehog Proteins; hedgehog inhibitor; cemiplimab; immunotherapy; Aged

Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636).In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability.Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths.Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.