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The PD-L1 antibody cosibelimab, when given at a fixed dose of 800 mg every 2 weeks, elicited a promising objective response rate with acceptable safety and tolerability in patients with metastatic cutaneous squamous cell carcinoma, meeting the primary end point of a phase 1 registration-enabling trial.
The PD-L1 antibody cosibelimab (formerly CK-301), when given at a fixed dose of 800 mg every 2 weeks, elicited a promising objective response rate (ORR) with acceptable safety and tolerability in patients with metastatic cutaneous squamous cell carcinoma (CSCC), meeting the primary end point of a phase 1 registration-enabling trial (NCT03212404).1
Topline data showed that among the 78 patients who were enrolled to the metastatic CSCC cohort of the trial, the immunotherapy elicited an ORR of 47.4% (95% CI, 36.0%-59.1%) per independent central review and RECIST v1.1 criteria. Moreover, the median duration of response (DOR) in these patients had not yet been reached, and 76% of patients had ongoing responses at the time of the data cutoff.
The safety of the agent was examined in 201 patients with advanced cancers who were enrolled to the trial and were treated across cohorts. The data reported proved to be consistent with prior reports on the agent, with most treatment-emergent toxicities noted to be only grade 1 or 2.
Based on these findings, Checkpoint Therapeutics, Inc., the drug developer, shared plans to submit a biologics license application to the FDA for cosibelimab later in 2022, which will be followed by the submission of a marketing authorization application in Europe along with other potential submissions on a global scale.
“These impressive results demonstrate that cosibelimab, a novel PD-L1 antibody with a unique two-fold mechanism of action, has the potential to offer physicians a new treatment option that provides compelling efficacy, complemented by a favorable tolerability profile, for patients living with this devastating disease,” Professor Philip Clingan, medical oncologist at Southern Medical Day Care Centre and co-principal investigator of the trial, stated in a press release.
The high affinity, fully human monoclonal antibody of IgG1 subtype was designed to directly bind to PD-L1 and block PD-L1 interaction with PD-1 and B7.1 receptors. The primary mechanism of action of the agent is based on the inhibition of the interaction between PD-L1 and these receptors, which eliminates the suppressive effects of PD-L1 on antitumor CD8-positive T cells and reinstates cytotoxic T-cell response.
The agent is thought to differ from other marketed PD-1 and PD-L1 therapies in that it has a sustained target tumor occupancy of greater than 99% which reactivates immune response; it also has a functional Fc domain that allows for the induction of antibody-dependent cell-mediated cytotoxicity, which can lead to better efficacy in select tumor types.
With the registration-enabling clinical trial, investigators set out to examine the safety, tolerability, and efficacy of cosibelimab monotherapy in patients with select recurrent or metastatic cancers such as CSCC, lung neoplasms, head and neck cancer, and non-Hodgkin lymphoma.2
The trial was comprised of 3 periods. In the first period, participants underwent screening for up to 28 days. In the second period, treatment was given in 28-day cycles. The third period, the follow-up period will persist for 6 months, and select patient cohorts with be followed for survival data. Following the dose-escalation portion of the research, additional patients may be included to further investigate the safety and efficacy of cosibelimab at certain doses or within certain subsets.
To be eligible for enrollment on any of the cohorts, patients needed to be at least 18 years of age. To participate in the CSCC cohort specifically, patients needed to have a histologically confirmed diagnosis of unresectable or metastatic disease that was not amenable to local therapy. Those who had received prior PD-1, PD-L1, PD-L2, CD137, or CTLA-4 agents, or any drugs that targeted T-cell costimulation or immune checkpoint pathways, were excluded.
The primary end point of the trial was confirmed ORR. Other important end points include confirmed best overall response, DOR, overall survival, safety, and several pharmacokinetic parameters.
At the 2020 SITC Annual Meeting, interim data were reported on the use of cosibelimab in those with CSCC and non–small cell lung cancer (NSCLC). In both subsets, the agent was found to produce robust, durable responses. In those with CSCC specifically, the agent elicited an ORR of 51.1% (95% CI, 36.1%-66.0%).3
Of the 24 patients who responded to treatment with the immunotherapy, 5 had a complete response and 19 experienced partial responses, 12 of which were confirmed. Moreover, 83% of these patients were noted to have continued responses to treatment. The median DOR and progression-free survival (PFS) had not yet been reached.
In the cohort of patients with NSCLC, the ORR achieved with cosibelimab was 44.0% (95% CI, 24.4%-65.1%), with a median DOR of 15.3 months (95% CI, 11.0-19.6), and a median PFS of 10.3 months (95% CI, 7.0-13.7).4
“We are thrilled to report these topline results from our pivotal trial of cosibelimab in metastatic CSCC,” James F. Olivero, president and chief executive officer of Checkpoint Therapeutics, Inc., stated in a press release. “We believe the strong ORR result is attributable to cosibelimab’s differentiated, two-fold mechanism of action of engaging both T cells and natural killer cells, while also demonstrating a potential favorable safety profile through binding to PD-L1, reported in literature as associated with lower rates of severe or worse adverse effects as compared with PD-1 therapy…We look forward to a detailed presentation of the data at an upcoming medical meeting.”
The company will continue to enroll patients to the CSCC cohort of the trial.
Cosibelimab is also under investigation in combination with pemetrexed and platinum chemotherapy in the first-line treatment of patients with nonsquamous NSCLC as part of the phase 3 COTERNO trial (NCT04786964), which was initiated in December 2021.5