Cosibelimab in advanced cutaneous squamous cell carcinoma (CSCC): Longer-term efficacy and safety results from pivotal study

Abstract

Background: Cosibelimab is a high-affinity, fully human monoclonal antibody that directly binds to programmed death ligand-1 (PD-L1) and blocks its interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors to restore an anti-tumor immune response. Cosibelimab also has a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) as an additional mechanism of anti-tumor immunity. Efficacy and safety data from a pivotal study (NCT03212404) supported a biologics license application for cosibelimab for the treatment of patients (pts) with advanced CSCC (metastatic [mCSCC] or locally advanced [laCSCC]) who are not candidates for curative surgery or radiation. Here, we present new longer-term follow-up data from the pivotal study. Methods: Pts with mCSCC (Group [Gp] 1) and laCSCC (Gp 2) were treated with cosibelimab 800 mg Q2W. The primary endpoint was objective response rate (ORR; complete response + partial response) by independent central review (ICR) assessed by Gp. The safety analysis included all CSCC pts treated with at least one dose and includes a third Gp of pts with mCSCC treated with cosibelimab 1200 mg Q3W (Gp 3). Results: As of the 31 March 2023 data cutoff, 192 pts were enrolled and treated (78 in Gp 1, 58 in Gp 2 and 56 in Gp 3), and 109 pts were eligible for long-term efficacy assessment (78 in Gp 1 and 31 in Gp 2). With a median duration of follow-up of 29.3 months (range: 0.4-52.0) for Gp 1 and 24.1 months (range: 2.8-37.3) for Gp 2, ORR per ICR was 50.0% (95% CI: 38.5-61.5) and 54.8% (95% CI: 36.0-72.7), respectively.The complete response rate was 12.8% and 25.8% for Gp 1 and 2, respectively. Median duration of response has not been reached in either Gp, with a probably of maintaining response at 24 months of 72.1% and 80.2% for Gp 1 and 2, respectively. The most common adverse events (AEs) by any grade (Gr) were fatigue (22.9%), anemia (20.3%), constipation (16.1%) and diarrhea (15.1%); Gr 3 were anemia (5.2%) and lipase increased (3.1%). 3.6% of pts experienced a Gr 3 immune-related AE (no Gr 4). Conclusions: Cosibelimab demonstrates robust objective response and complete response rates in advanced CSCC, with manageable safety and notable low rates of overall and severe immune-related AEs.