FDA Greenlights Cosibelimab in Metastatic or Locally Advanced CSCC

• The FDA has approved cosibelimab (formerly CK-301) for metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC).
• Findings from Study CK-301-101 (NCT03212404) support this regulatory decision.
• In the cohort of 78 patients with metastatic cSCC treated with cosibelimab, the objective response rate (ORR) at a median follow-up of 15.4 months (range, 0.4-40.5) was 47.4% (95% CI, 36.0%-59.1%).

Cosibelimab, an anti–PD-L1 antibody, has been approved by the FDA for the treatment of patients with metastatic or locally advanced cSCC that is not eligible for curative surgery or radiation.¹

This approval was supported by findings from Study CK-301-101. According to data published in October 2023 in the Journal for ImmunoTherapy of Cancer, the ORR at a median follow-up of 15.4 months (range, 0.4-40.5) was 47.4% (95% CI, 36.0%-59.1%) among those treated with cosibelimab.² The median duration of response was not reached (range, 1.4+ to 34.1+ months). Additionally, there was an ongoing response reported in 73% of patients.

Concept illustration of skin cancer

For safety, the most common treatment-emergent adverse events (AEs) seen in 15% of patients or more included fatigue (26.9%), rash (16.7%), and anemia (15.4%). Immune-related AEs were observed in 23.1% of patients. A total of 2.6% of these patients had grade 3 immune-related AEs, and there were no grade 4 or 5 immune-related AEs reported. Further, there were no treatment-related deaths in the study.

About Cosibelimab

In December 2023, the FDA issued a complete response letter (CRL) of the biologics licencse application (BLA) for cosibelimab. The CRL was issued following a multisponsor inspection of the third-party manufacturing organization and cited “approvability issues” to be addressed in the BLA resubmission. No concerns were presented regarding the clinical data package, safety, or labeling of the drug.^3,4

Originally, the FDA accepted the BLA of cosibelimab for filing in March 2023, based on findings from the registration-enabling phase 1 Study CK-301-101 trial. The open-label, multicenter, dose-escalation trial, enrolled patients across study sites in Australia, France, New Zealand, Poland, Russia, South Africa, Spain, Thailand, and Ukraine. Patients were given intravenous cosibelimab alone for 28-day cycles.

Enrollment in phase 1 of the study was open to patients aged 18 years and older with histologically confirmed metastatic cSCC that was not amenable to surgery. Patients must have also had an ECOG performance status of 0 to 1 and had a life expectancy of longer than 3 months.

Once enrolled, they were treated with intravenous cosibelimab at 800 mg every 2 weeks until confirmed complete response (CR), progressive disease, unacceptable toxicity, or clinical deterioration. After treatment, they entered follow-up.

The coprimary end points of the trial included dose-limiting toxicities, the number of patients who have treatment-emergent AEs, and the confirmed ORR. The secondary end points included confirmed best ORR, duration of response, overall survival, pharmacokinetics, and the number of patients with anti-cosibelimab antibodies.

In July 2024, the BLA of cosibelimab for metastatic or locally advanced cutaneous squamous cell carcinoma was resubmitted to the FDA.

Previously, in July 2023, Checkpoint Therapeutics announced longer-term data showing that cosibelimab had a deepened response over time, with a 55% ORR and 26% CR rate in locally advanced cSCC and a 50% ORR and 13% CR rate in metastatic cSCC.³

REFERENCES:

1. FDA approves cosibelimab-ipdl for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. December 13, 2024. Accessed December 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cosibelimab-ipdl-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma

2. Clingan P, Ladwa R, Brungs D, et al. Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma. J Immunother Cancer. 2023;11(10):e007637. doi:10.1136/jitc-2023-007637

3. Checkpoint Therapeutics announces biologics license application resubmission for cosibelimab. News release. Checkpoint Therapeutics. July 2, 2024. Accessed November 7, 2024. https://tinyurl.com/4a2aej3r

4. US Food and Drug Administration issues complete response letter for cosibelimab solely due to inspection findings at third-party manufacturer. News release. Checkpoint Therapeutics, Inc. December 18, 2023. Accessed November 7, 2024. https://tinyurl.com/5djvexw5