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

• DOI: 10.1136/jitc-2023-007637
• Publication Date: 2023-10-17T23:35:20Z
• Authors: Philip Clingan; Rahul Ladwa; Daniel Brungs; Dean Laurence Harris; Margaret McGrath; Susan Arnold; Jermaine Coward; Samuel Fourie; Andriy Kurochkin; Daniel R Malan; Andrew Mant; Vinay Sharma; Hong Shue; Andrea Tazbirkova; Miguel-Angel Berc...; Chaiyut Charoentum; Stéphane Dalle; Arunee Dechaphunkul; Oleksandr Dudnich...; Piotr Koralewski; Iwona Lugowska; Henri Montaudié; Eva Muñoz-Couselo; Virote Sriuranpong; James Oliviero; Jayesh Desai
• Keywords: Skin Neoplasms; Programmed Cell Death 1 Receptor; B7-H1 Antigen; :Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous Cell [DISEASES]; Humans; :Other subheadings::/therapeutic use [Other subheadings]; :neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::carcinoma de células escamosas [ENFERMEDADES]; Immune Checkpoint Inhibitors; :aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales [COMPUESTOS QUÍMICOS Y DROGAS]; RC254-282; Clinical/Translational Cancer Immunotherapy; Anticossos monoclonals - Ús terapèutic; :Otros calificadores::/uso terapéutico [Otros calificadores]; :diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Antibodies, Monoclonal; 16. Peace & justice; :Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]; 3. Good health; Pell - Càncer - Tractament; Avaluació de resultats (Assistència sanitària); Carcinoma, Squamous Cell; :Neoplasms::Neoplasms by Site::Skin Neoplasms [DISEASES]; :neoplasias::neoplasias por localización::neoplasias cutáneas [ENFERMEDADES]; Immunotherapy; :Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal [CHEMICALS AND DRUGS]

BackgroundProgrammed 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.MethodsIn 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.ResultsObjective 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.ConclusionsCosibelimab demonstrated clinically meaningful ORR and DOR and was associated with a manageable safety profile.Trial registration numberNCT03212404.