FDA Accepts Resubmitted BLA for Cosibelimab in Advanced Skin Cancer

Supporting data for cosibelimab in this indication came from the metastatic CSCC cohort of a phase 1 trial (NCT03212404). Efficacy and safety findings from this study were published in the Journal for ImmunoTherapy of Cancer.

The FDA has accepted a resubmitted biologics license application (BLA) for cosibelimab (CK-301) as a treatment for adult patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) not eligible to undergo curative radiotherapy or surgery, according to a press release from the developer, Checkpoint Therapeutics, Inc.¹

The regulatory agency has set a Prescription Drug User Fee Act date of December 28, 2024, for its decision on approving cosibelimab in the aforementioned indication.

Developers originally submitted a BLA seeking approval for cosibelimab as a treatment for CSCC in January 2023.² The FDA then sent a complete response letter (CRL) for cosibelimab in December 2023.³ Although the agency did not highlight any issues associated with the clinical data, safety, or labeling for cosibelimab, the letter noted insufficiencies after a multi-sponsor inspection of a third-party manufacturing site.

Developers resubmitted the BLA for cosibelimab in CSCC earlier in July 2024.⁴ The agency has accepted the resubmitted BLA as a complete response to the concerns highlighted in its previous CRL.

“We are pleased that the FDA has accepted our BLA resubmission as a complete response after we aligned on our BLA resubmission strategy,” James F. Oliviero, president and chief executive officer at Checkpoint Therapeutics, said in the press release.¹ “We look forward to working closely with the FDA to finalize the review and to the potential opportunity to deliver cosibelimab’s unique dual mechanism of action to patients [with] CSCC.”

Supporting data for cosibelimab in this indication came from the metastatic CSCC cohort of a phase 1 trial (NCT03212404). Efficacy and safety findings from this study were published in the Journal for ImmunoTherapy of Cancer.⁵

Treatment with cosibelimab yielded a confirmed objective response rate (ORR) of 47.4% (95% CI, 36.0%-59.1%) across the intent-to-treat population while eliciting robust, enduring target lesion reductions. The median observed time to response was 1.9 months (range, 1.6-6.6), and the median duration of response (DOR) was not reached (range, 1.4+ to 34.1+ months). Ongoing responses were reported in 73.0% of responders at the time of data cutoff.

Data also showed an ORR of 45.9% (n = 17/37) per independent central review (ICR) among patients with PD-L1–positive disease. Additionally, the ORR was 44.4% (n = 8/18) in those with PD-L1–negative tumors. Enduring responses occurred regardless of PD-L1 status.

Frequent treatment-emergent adverse effects (TEAEs) included fatigue (26.9%), rash (16.7%), and anemia (15.4%). Additionally, 11.5% of patients discontinued study treatment due to AEs, with 2.6% of these toxicities being attributable to cosibelimab. The most common grade 3 or higher AE was anemia (6.4%).

Investigators reported that 3.8% (n = 3) of patients died due to AEs, with all events being unrelated to treatment with cosibelimab. Causes of death included COVID–19–related illness (n = 2) and cardiac arrest following a history of cardiovascular disease (n = 1). Immune-related AEs affected 23.1% of patients, and 2.6% experienced grade 3 toxicities of this type.

Patients enrolled on this open-label, multicenter, multicohort trial received a fixed dose of cosibelimab at 800 mg intravenously every 2 weeks until a confirmed complete response, disease progression, toxicity, or clinical deterioration.

The trial’s prespecified primary end point was ORR based on ICR using RECIST v1.1 criteria. Secondary end points included DOR and incidence and severity of TEAEs.

Patients 18 years and older with an ECOG performance status of 0 or 1 and a minimum life expectancy of 3 months were eligible for enrollment on the trial. Those with severe hypersensitivity to other monoclonal antibodies, prior treatment with immune checkpoint inhibitors, or prior autoimmune disease were ineligible for study entry.

References

1. Checkpoint Therapeutics announces FDA acceptance of BLA resubmission of cosibelimab for the treatment of advanced cutaneous squamous cell carcinoma. News release. Checkpoint Therapeutics, Inc. July 25, 2024. Accessed July 26, 2024. https://tinyurl.com/mr33hn7z
2. Checkpoint Therapeutics submits biologics license application to FDA for cosibelimab as a treatment for patients with metastatic or locally advanced cutaneous squamous cell carcinoma. News release. Checkpoint Therapeutics, Inc. January 4, 2023. Accessed July 26, 2024. yhoo.it/3GqykPg
3. U.S. 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 26, 2024. https://tinyurl.com/5yewpx4b
4. Checkpoint Therapeutics announces biologics license application resubmission for cosibelimab. News release. Checkpoint Therapeutics, Inc. July 2, 2024. Accessed July 2, 2024. https://tinyurl.com/mvf8ae5p
5. 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