Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma

Abstract

Background: Programmed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity programmed cell death-ligand 1 (PD-L1)-blocking antibody that activates innate and adaptive immunity by blocking PD-L1 interaction with PD-1 and B7-1 receptors. It is an unmodified immunoglobulin G1 subtype with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Here, we present results of the pivotal study of patients with metastatic CSCC from an open-label, multicenter, multiregional, multicohort, phase 1 trial of cosibelimab.

Methods: In this trial, participants with metastatic CSCC received cosibelimab 800 mg intravenously every 2 weeks. Primary endpoint was objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, V.1.1. Secondary endpoints included duration of response (DOR) and safety.

Results: Objective response was observed in 37 of 78 participants (47.4% (95% CI: 36.0% to 59.1%)), with median follow-up of 15.4 months (range: 0.4 to 40.5) as of data cut-off. Median DOR was not reached (range: 1.4+ to 34.1+ months), with response ongoing in 73.0% of participants. Common treatment-emergent AEs (≥15%) were fatigue (26.9%), rash (16.7%), and anemia (15.4%). Eighteen participants (23.1%) experienced immune-related AEs (grade 3: n=2 (2.6%); no grade 4/5). No treatment-related deaths were reported.

Conclusions: Cosibelimab demonstrated clinically meaningful ORR and DOR and was associated with a manageable safety profile.

Trial registration number: NCT03212404.

Keywords: Immune Checkpoint Inhibitors; Immunotherapy; Programmed Cell Death 1 Receptor; Skin Neoplasms.

Figure 1

mCSCC best overall response to cosibelimab monotherapy. Best percentage change in the sum of target lesion diameters from baseline for participants who underwent tumor assessment by independent central review after treatment initiation (n=70). Figure excludes participants with a best overall response of not evaluable due to no post-baseline tumor assessment (n=8), which are included as non-responders in the calculation of ORR. Horizontal dashed lines indicate RECIST V.1.1 criteria for partial response (≥30% decrease in the sum of target lesion diameters) and progressive disease (≥20% increase in target lesion diameters). mCSCC, metastatic cutaneous squamous cell carcinoma; ORR, objective response rate; RECIST V.1.1, Response Evaluation Criteria in Solid Tumors, version 1.1.

Figure 2

Effect of cosibelimab on time to response, DOR, and an individual case. (A) Time to response and DOR in responding participants who underwent tumor assessment by independent central review after treatment initiation (n=37). (B) Effect of cosibelimab monotherapy in a participant with mCSCC. An adult patient with a CSCC skin lesion at the right postauricular region at baseline (left), after 8 weeks (middle), and after 26 weeks (right) of treatment initiation with cosibelimab. CSCC, cutaneous squamous cell carcinoma; DOR, duration of response; mCSCC, metastatic CSCC.