Cosibelimab: An Anti-PD-L1 Antibody

Cosibelimab (CK-301) is an investigational fully-human monoclonal antibody that binds programmed death-ligand 1 (PD-L1) and blocks its interaction with Programmed cell death protein 1 (PD-1). PD-1 and its ligand PD-L1 are checkpoints of immune activation and play a very important role in negative regulation of T-cell effector function and proliferation. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptor PD-1, which removes the suppressive effects of PD-L1 on anti-tumor T-cells to restore the cytotoxic T-cell response. Additionally, cosibelimab has a functional Fc domain that may be capable of inducing antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells.

Targeting the PD-1/PD-L1 pathway using a monoclonal antibody has proven to be effective in many oncological indications as a monotherapy or in combination with other anti-tumor immune response potentiating compounds and targeted therapies. Checkpoint licensed the exclusive worldwide rights to cosibelimab from Dana-Farber Cancer Institute in March 2015.

Cosibelimab is being evaluated in a global, open-label, multicohort Phase 1 clinical trial in checkpoint therapy-naïve patients with selected recurrent or metastatic cancers, including ongoing cohorts in locally advanced and metastatic cutaneous squamous cell carcinoma (cSCC) intended to support one or more applications for marketing approval. Checkpoint is also undertaking a global, randomized Phase 3 (CONTERNO) trial of cosibelimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with non-squamous non-small cell lung cancer.

Cosibelimab in Metastatic Cutaneous Squamous Cell Carcinoma (cSCC)

In January, 2022, Checkpoint announced positive topline results from a registration-enabling Phase 1 clinical trial evaluating the safety and efficacy of its anti-PD-L1 antibody, cosibelimab, administered as a fixed dose of 800 mg every two weeks in patients with metastatic cSCC.

The study met its primary endpoint, with cosibelimab demonstrating a confirmed objective response rate (ORR) of 47.4% (95% CI: 36.0, 59.1) based on independent central review of 78 patients enrolled in the metastatic cSCC cohort using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria. Based on these results, Checkpoint intends to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration for cosibelimab later in 2022, to be followed by a marketing authorization application (MAA) submission in Europe and additional potential submissions in markets worldwide.

Cosibelimab in Non-squamous Non-small Cell Lung Cancer (NSCLC)

In December 2021, Checkpoint announced the initiation of the CONTERNO study, a global, randomized Phase 3 trial of cosibelimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with non-squamous non-small cell lung cancer (NSCLC). The primary endpoint for the CONTERNO Phase 3 trial is overall survival (OS), and the study is designed to support full regulatory approvals worldwide.

The CONTERNO study (ClinicalTrials.gov, NCT04786964) is a Phase 3, open-label, multi-center, randomized trial investigating cosibelimab (1200 mg every three weeks) combined with pemetrexed and investigator’s choice of platinum chemotherapy (either carboplatin or cisplatin) versus pemetrexed and platinum chemotherapy alone in patients with previously untreated stage IV non-squamous NSCLC and with no EGFR mutations or ALK translocations. The primary endpoint is OS. Key secondary endpoints include progression-free survival, objective response rate and safety. Approximately 560 subjects will be randomized in a 2:1 ratio to receive cosibelimab in combination with chemotherapy or chemotherapy alone.