Cosibelimab Continues to Show Promise in Locally Advanced Cutaneous Squamous Cell Carcinoma

The PD-L1 antibody cosibelimab (formerly CK-301) was found to elicit an encouraging objective response rate (ORR) in patients with locally advanced cutaneous squamous cell carcinoma (CSCC) who were not eligible to undergo curative surgery or radiation, according to interim data from a phase 1 registration-enabling trial (NCT3212404).¹

As of the March 2022 data cutoff, the agent elicited an ORR of 54.8% (95% CI, 36.0%-72.7%) per independent central review (ICR) in 31 patients, which substantially exceeded a clinically meaningful lower bound of the 95% two-sided confidence interval of 25%.

In light of these positive findings, Checkpoint Therapeutics, Inc., the drug developer, shared plans to continue discussions with the FDA on the potential addition of locally advanced CSCC as a second indication for the agent in the planned biologics license application that is slated for submission later this year.

“These exciting positive interim results in this cohort of patients suggest a potential second indication for cosibelimab in locally advanced CSCC, which, when added to the potential labeling in the metastatic CSCC setting, could double the market opportunity at launch for cosibelimab globally,” James Olivero, president and chief executive officer of Checkpoint Therapeutics, Inc., stated in a press release.

Cosibelimab is a high affinity, fully human monoclonal antibody of IgG1 subtype that directly binds to PD-L1; the agent blocks PD-L1 interaction with PD-1 and B7.1 receptors. The primary mechanism of action of the agent is based on inhibition of the interaction between PD-L1 and these receptors, which eradicates the suppressive effects of PD-L1 on antitumor CD9-positive T cells and restores cytotoxic T-cell response.

The registration-enabling clinical trial was launched to assess the safety and tolerability, as well as the efficacy, of single-agent cosibelimab in patients with select recurrent or metastatic cancers like CSCC, lung neoplasms, head and neck cancer, and non-Hodgkin lymphoma.²

To participate in any of the cohorts of the trial, patients were required to be at least 18 years of age. To enroll in the CSCC cohort, they needed to have a histologically confirmed diagnosis of unresectable or metastatic disease that was not amenable to local therapy. Those who previously received PD-1, PD-L1, PD-L2, CD137, or CTLA-4 agents, or any drugs that targeted T-cell co-stimulation or immune checkpoint pathways, were excluded.

The trial was made up of 3 periods. In the first period, patients were screened for up to 28 days. They received treatment in the second period, and this was administered in 28-day cycles. The third period, or the follow-up period, will continue or 6 months; here, select cohorts will be followed to collect survival data. After the dose-escalation portion of the trial, additional patients may be enrolled to further evaluate the safety and efficacy of cosibelimab at select doses or within certain subsets.

The primary end point of the trial was confirmed ORR, and other end points included confirmed best overall response, duration of response (DOR), overall survival, safety, and pharmacokinetics.

In January 2022, the company shared topline findings from the trial, which showed that when the agent was administered at a fixed dose of 800 mg every 2 weeks, it elicited an ORR of 47.4% (95% CI, 36.0%-59.1%) per IRC and RECIST v1.1 criteria in patients with metastatic CSCC (n = 78).³ The median DOR had not yet been reached, and 76% of patients were still responding to treatment at the time of the data cutoff.

In 201 patients with advanced cancers enrolled to the trial and treated across cohorts, safety data with the agent were noted to be consistent with previous reports on cosibelimab. Most treatment-emergent adverse effects (AEs) were grade 1 or 2 in severity.

Prior data shared at the 2020 SITC Annual Meeting indicated that cosibelimab produced robust durable responses in those with CSCC and those with non–small cell lung cancer (NSCLC). Specifically, in those with CSCC, the agent induced an ORR of 51.1% (95% CI, 36.1%-66.0%).⁴

Of the 24 responders, 5 achieved a complete response and 19 experienced partial responses, 12 of which were confirmed. Most patients (83%) were noted to have continued responses to treatment, and the median DOR and progression-free survival (PFS) in these patients had not yet been reached.

In the NSCLC cohort, cosibelimab resulted in an ORR of 44.0% (95% CI, 24.4%-65.1%), with a median DOR of 15.3 months (95% CI, 11.0-19.6). The median PFS reported in this cohort with cosibelimab was 10.3 months (95% CI, 7.0-13.4).⁵

“We believe the data generated to date continue to show cosibelimab as a differentiated and potentially best-in-class, anti–PD-1 antibody, leveraging a 2-fold mechanism of action to deliver robust efficacy with a potentially more favorable safety profile due to its binding to PD-L1 rather than PD-1, an attribute reported in scientific literature as associated with lower rates of severe or worse AEs as compared with anti–PD-1 therapy,” Oliviero added in the release.

References

1. Checkpoint Therapeutics announces positive interim results from registration-enabling trial of cosibelimab in locally advanced cutaneous squamous cell carcinoma. News release. Checkpoint Therapeutics, Inc. June 16, 2022. Accessed June 16, 2022. https://bit.ly/3aTUIUQ
2. Phase 1 study of CK-301 (cosibelimab) as a single agent in subjects with advanced cancers. ClinicalTrials.gov. Accessed January 13, 2022. Accessed June 16, 2022. https://clinicaltrials.gov/ct2/show/NCT03212404
3. Checkpoint Therapeutics announces positive topline results from the registration-enabling trial of cosibelimab in metastatic cutaneous squamous cell carcinoma. News release. Checkpoint Therapeutics, Inc. January 25, 2022. Accessed June 16, 2022. https://bit.ly/3IC0nKV
4. Harris DL, Brungs D, Ladwa R, et al. Cosibelimab, an anti-PD-L1 antibody: preliminary safety and efficacy results from a global, multicohort phase 1 clinical trial. Journal for ImmunoTherapy of Cancer. 2020;8. doi:10.1136/jitc-2020-SITC2020.0399
5. Clingan PR, Brungs D, Ladwa R, et al. Cosibelimab, an anti-PD-L1 antibody in metastatic cutaneous squamous cell carcinoma (CSCC): preliminary safety and efficacy results from a phase 1 clinical trial. Ann Oncol. 2020;31(suppl 4):S736. doi:10.1016/j.annonc.2020.08.1208