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.
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.
In June, 2022, Checkpoint announced positive interim results from its registration-enabling trial of cosibelimab in locally advanced cSCC. As of the March, 2022, data cutoff, the ORR determined by independent central review in 31 patients was 54.8% (95% CI: 36.0, 72.7), exceeding a clinically meaningful lower bound of the 95% two-sided confidence interval of 25%.
Based on these results, in January, 2023, Checkpoint submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for cosibelimab as a treatment for patients with metastatic cSCC or locally advanced cSCC who are not candidates for curative surgery or radiation.
In June, 2023, Checkpoint presented new pharmacokinetic (PK) modeling data on cosibelimab supporting the commercial extended interval dosing regimen proposed in the BLA of 1200 mg every three weeks (Q3W), which has been shown to be equivalent to 800 mg every two weeks (Q2W).
In July, 2023, Checkpoint announced that longer-term data in its pivotal studies for cosibelimab in locally advanced and metastatic cSCC demonstrated a deepening of response over time, resulting in substantially higher complete response rates than previously reported. Furthermore, responses continued to remain durable over time, with the median duration of response not yet reached in either group. As of the data cutoff in January, 2023, the confirmed ORR in metastatic cSCC was 50% (95% CI: 38.5, 61.5) and 55% (95% CI: 36.0, 72.7) in locally advanced cSCC.
In October, 2023, the Journal for ImmunoTherapy of Cancer (JITC), the peer-reviewed, online journal of the Society of Immunotherapy of Cancer, published a paper entitled, “Efficacy and Safety of Cosibelimab, an Anti–PD-L1 Antibody, in Metastatic Cutaneous Squamous Cell Carcinoma” (doi:10.1136/jitc-2023-007637), based on results from Checkpoint’s pivotal trial evaluating cosibelimab in patients with metastatic cSCC.
In December, 2023, Checkpoint announced the FDA issued a complete response letter (CRL) for the cosibelimab BLA due solely to inspection findings that arose during a multi-sponsor inspection of Checkpoint’s third-party contract manufacturing organization as approvability issues to address in a resubmission.
Checkpoint resubmitted its BLA for cosibelimab in July, 2024. The FDA accepted the resubmission and has set a Prescription Drug User Fee Act (“PDUFA”) goal date of December 28, 2024.
With its unique mechanism of action and compelling safety profile, cosibelimab, if approved, may be uniquely positioned to provide an important new treatment option for cSCC patients currently underserved by available therapies, particularly for the significant number of cSCC patients with immunosuppressive conditions or autoimmune diseases.
Checkpoint intends to submit a marketing authorization application (MAA) submission in Europe and additional potential submissions in markets worldwide.