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.