Checkpoint Therapeutics, Inc. announced the publication of results from the multicenter, multiregional, pivotal trial evaluating cosibelimab, a differentiated and potential best-in-class anti-PD-L1 antibody, in patients with metastatic cutaneous squamous cell carcinoma (?cSCC?), in the Journal for ImmunoTherapy of Cancer (JITC), the peer-reviewed, online journal of the Society of Immunotherapy of Cancer. The paper, entitled, ?Efficacy and Safety of Cosibelimab, an Anti?PD-L1 Antibody, in Metastatic Cutaneous Squamous Cell Carcinoma? (doi:10.1136/jitc-2023-007637), describes safety and efficacy results from 78 patients with metastatic cSCC enrolled at clinical sites in eight countries.

Patients received cosibelimab 800 mg every two weeks as an intravenous infusion until disease progression or unacceptable toxicity. The study?s primary endpoint was objective response rate (?ORR?) assessed by independent central review using Response Evaluation Criteria in Solid Tumors, v.1.1. As of the pre-specified data cutoff date, the primary endpoint was met with highly clinically meaningful results. Median duration of response was not yet reached.

The authors observed that cosibelimab treatment was associated with lower rates of severe immune-related adverse events (?irAEs?) as compared with those reported for similar studies of PD-1-targeting agents, concluding that cosibelimab may address an area of unmet clinical need for effective and better tolerated treatments for patients with metastatic cSCC who are ineligible for curative surgery or radiation. Cutaneous squamous cell carcinoma is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1 million cases according to the Skin Cancer Foundation. While most cases are localized tumors amenable to curative resection, approximately 40,000 cases will become advanced, and an estimated 15,000 people will die from their disease each year.

In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear. Cosibelimab is a potential best-in-class, high affinity, fully human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 (?PD-L1?) and blocks the PD-L1 interaction with the programmed death receptor-1 (?PD-1?) and B7.1 receptors. Cosibelimab?s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response.

Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained >99% target tumor occupancy to reactivate an antitumor immune response and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity (?ADCC?) for potential enhanced efficacy in certain tumor types.