Cosibelimab Under Investigation in Metastatic Cutaneous Squamous Cell Carcinoma

James F. Oliviero

The anti–PD-L1, fully human monoclonal antibody cosibelimab (formerly, CK-301) will be examined in a cohort of patients with metastatic cutaneous squamous cell carcinoma (CSCC) as part of an ongoing phase 1 study (NCT03212404).^1,2

The registration-enabling clinical trial is examining the safety, tolerability, and efficacy of cosibelimab as an intravenously-administered single agent in patients with selected recurrent or metastatic cancers.

Previously, in January 2020, the FDA confirmed the registration submission pathway for the examination of the agent in patients with metastatic CSCC; in May 2021, enrollment to this cohort was completed.

“We are pleased to report the completion of enrollment for our metastatic CSCC cohort, with over 75 patients enrolled, which we expect will enable a readout of topline results in the fourth quarter of this year,” James F. Oliviero, president and chief executive officer of Checkpoint Therapeutics, Inc., stated in a press release.

Cosibelimab is a IgG1 monoclonal antibody subtype that binds to PD-L1 and blocks its interaction with PD-1 and B7.1 to induce an antitumor response. Moreover, cosibelimab is potentially differentiated from the PD-1 and PD-L1 antibodies that are currently on the market through sustained target tumor occupancy of greater than 99% that allows it to reactivate an antitumor immune response. The agent also has the additional benefit of a functional Fc domain that is able to induce antibody-dependent, cell-mediated cytotoxicity that could result in stronger efficacy for certain tumor types.

In the phase 1 study, investigators are examining cosibelimab in several malignancies in addition to CSCC, including lung neoplasms, head and neck cancer, and non-Hodgkin lymphoma.

The first-in-human, open-label multicenter, dose-escalation study is comprised of 3 periods. In the first period, patients will undergo screening for up to 28 days; this will be followed by the second period, in which treatment which will be administered in 28-day cycles. The follow-up period will last for 6 months with a survival follow-up for select patient cohorts. After the dose-escalation portion of the study, additional evaluable patients may be included to further understand the safety and efficacy of cosibelimab at select doses or within certain subsets.

The trial enrolled patients at least 18 years of age across all cohorts. To enroll to the CSCC cohort, patients needed to have a histologically confirmed diagnosis of unresectable or metastatic CSCC that was not amenable to local therapy.

Any patients who had previously been treated with PD-1, PD-L1, PD-L2, CD137, or CTLA-4 agents, as well as any drugs that target T-cell costimulation or immune checkpoint pathways, were excluded from the trial. Additionally, if a patient had received concurrent treatment with a non-permitted agent, a history of severe hypersensitivity reactions to other monoclonal antibodies, or a prior active malignancy within the past 2 years with the exception of locally curable disease, they could not participate.

The primary objectives of the trial included confirmed objective response rate (ORR), determining the incidence of dose-limiting toxicities, and the number of patients who experienced treatment-emergent adverse effects. Key secondary objectives included confirmed best overall response, duration of response (DOR), overall survival, and several pharmacokinetic parameters.

Findings from the CSCC cohort are anticipated to read out in the fourth quarter of 2021. If positive, Checkpoint Therapeutics, Inc., shared plans to submit a biologics license application for the agent to the FDA in the first half of 2022; the company will also submit a Marketing Authorization Application for the agent in Europe.

Interim data on the use of cosibelimab in patients with non–small cell lung cancer and CSCC shared during the 2020 SITC Annual Meeting revealed that the agent elicited durable and robust responses in both patient subsets. Specifically, in the patients with locally advanced or metastatic CSCC, cosibelimab induced an ORR of 51.1% (95% CI, 36.1%-66.0%).

Of the 24 responders, 5 achieved complete responses to cosibelimab, while 19 experienced partial responses (PRs), 12 of which were confirmed. Eighty-three percent of patients within the cohort experienced ongoing responses to treatment. Moreover, the median DOR and progression-free survival (PFS) with the agent had not yet been reached. These findings were previously presented during the 2020 ESMO Virtual Congress.³

The agent also induced an ORR of 44.0% (95% CI, 24.4%-65.1%) in the NSCLC cohort.⁴ Patients in this subset experienced a median DOR of 15.3 months (95% CI, 11.0-19.6) with cosibelimab, with a median PFS of 10.3 months (95% CI, 7.0-13.7).

“Based on the interim data presented last year at the 2020 ESMO Virtual Congress and the [virtual] SITC Annual Meeting, we believe cosibelimab has the potential to be a best-in-class anti–PD-L1 antibody, which we intend to commercialize at a substantially lower price in comparison to currently marketed anti–PD-[L]1 therapies,” Oliviero added in the release. “With a compelling safety and efficacy profile, as well as our market-disruptive pricing strategy, we believe cosibelimab can achieve meaningful and rapid market share in the $25 billion and growing PD-[L]1 class.”

References

1. Checkpoint Therapeutics announces completion of enrollment in the registration-enabling trial of cosibelimab in metastatic cutaneous squamous cell carcinoma. News release. Checkpoint Therapeutics, Inc. May 12, 2021. Accessed May 17, 2021. https://bit.ly/33VbpbC
2. Phase 1 study of CK-301 (cosibelimab) as a single agent in subjects with advanced cancers. ClinicalTrials.gov. Updated March 16, 2021. Accessed May 17, 2021. https://clinicaltrials.gov/ct2/show/NCT03212404
3. 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
4. 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