Cosibelimab BLA Resubmitted to FDA for Metastatic cSCC

• The biologics license application (BLA) of cosibelimab (formerly CK-301) for metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC) has been resubmitted to the FDA.
• The FDA issued a complete response letter (CRL) to the application in December 2023.
• The CRL was in response to inspection findings at the drug’s manufacturing facility.

The BLA of cosibelimab, an anti-PD-L1 antibody, for the treatment of metastatic or locally advanced cSCC that is not eligible for curative surgery or radiation has been resubmitted to the FDA following a CRL that was issued in December 2023, according to Checkpoint Therapeutics.¹

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; however, there were no concerns presented regarding the clinical data package, safety, or labeling of the drug.^1,2

Findings from Study CK-301-101 (NCT03212404) support the BLA.³ Data from the phase 1 study were published in October 2023 in the Journal for ImmunoTherapy of Cancer and showed an objective response rate (ORR) of 47.4% (95% CI, 36.0%-59.1%) at a median follow-up of 15.4 months (range, 0.4-40.5).⁴ The median duration of response was not reached (range, 1.4+ to 34.1+ months), and an ongoing response was reported in 73% of patients.

The most common treatment-emergent adverse events (AEs) occurring in at least 15% of patients were fatigue (26.9%), rash (16.7%), and anemia (15.4%). Immune-related AEs were reported in 23.1% of patients, with 2.6% reporting grade 3 immune-related AEs. No grade 4 or 5 immune-related AEs were observed, and no treatment-related deaths were reported.

“From a safety profile perspective, both a scientifically plausible rationale and reasonable evidence from published clinical data support the premise that certain serious toxicities known to occur with available anti-PD-1 antibodies can be avoided with the anti-PD-L1 antibody cosibelimab, possibly owing to the presence of the other PD-1 ligand, PD-L2, which may maintain some level of checkpoint signaling,” study authors wrote.

In July 2023, Checkpoint Therapeutics announced longer-term data showing that cosibelimab had a deepened response over time, with a 55% ORR and 26% complete response (CR) rate in locally advanced cSCC and a 50% ORR and 13% CR rate in metastatic cSCC.¹

REFERENCES:

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

2. 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 July 2, 2024. https://tinyurl.com/5djvexw5

3. 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 July 2, 2024. https://tinyurl.com/5djvexw5

4. 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