Alexander Stratigos, M.D., Professor of Dermatology/Or Investigator of the University of Athens Medical School at Andreas Sygros Hospital explains the ESMO 2020 Abstract on Primary analysis of phase II results for cemiplimab in patients (pts) with locally advanced basal cell carcinoma (laBCC) who progress on or are intolerant to hedgehog inhibitors (HHIs).
There is no approved post-HHI therapeutic option for LaBCC pts. Cemiplimab, a PD-1 antibody, is a proven drug approved for the treatment of advanced cutaneous squamous cell carcinoma (CSCC) in patients who are not candidates for curative surgery or radiation therapy. Both BCC and CSCC, due to ultraviolet mutagenesis, are keratinocytic tumors with a heavy mutational burden and are theoretically vulnerable to immunotherapy. The primary review of the laBCC cohort from the seminal phase II cemiplimab second-line (or greater) setting study is presented.
Cemiplimab 350 mg Q3W IV was administered to Pts with laBCC (for up to 93 weeks or until progression). The primary endpoint was the Independent Central Analysis (ICR) objective response rate (ORR). Secondary goals included safety and tolerability evaluation, Length of Reaction (DOR) calculation, progression-free survival (PFS), and overall survival ( OS). Two responses verified after the data cut-off date of 17 February 2020 were included in the ORR.
84 pts were registered; 66.7% were male; the mean age was 70 years ( range: 42-89). The median follow-up period was 15 (range: 0.5-25) months. 31 percent (95 percent CI: 21-42) was ORR per ICR, including five absolute responses and 21 partial responses. Median DOR was not achieved; at 12 months, according to the Kaplan-Meier process, an estimated 85 percent of responses were ongoing. The median PFS and OS were not achieved. The median PFS was 19 months for all patients. Fatigue (30 percent), diarrhoea (24 percent), and pruritus (21 percent) were the most common adverse effects (AEs); 17 percent of patients stopped care because of AEs. The median baseline tumour mutational burden (TMB) between responding (n=18) and non-responding (n=38) pts was 58.2 and 23.5 mutations / Mb, respectively, but responses occurred at all TMB stages. In non-responding BCCs with high TMB, exploratory biomarker analysis established downregulation of major histocompatibility complex-I expression as a possible immune evasion mechanism.
Cemiplimab is the first therapeutic benefit agent for laBCC pts that are improving or intolerant to HHI treatment, regardless of biomarker status.
Identification for a clinical trial-