FDA Accepts Resubmission of BLA for Cosibelimab in Locally Advanced or Metastatic CSCC

FDA

The FDA has accepted the resubmission of a biologics license application (BLA) seeking the approval of cosibelimab (CK-301) for the treatment of patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.¹

The BLA, which was resubmitted on July 2, 2024, has been accepted as a complete response to address the deficiencies detailed in the FDA’s complete response letter (CRL) issued in December 2023. The CRL cited issues arising from a multi-sponsor inspection of a third-party contract manufacturing organization employed by Checkpoint Therapeutics, the developer of cosibelimab. However, it did not state any concerns regarding the clinical data package, safety, or labeling of cosibelimab.^1,2

In June 2024, Checkpoint Therapeutics announced that it had aligned with the FDA on a strategy to address these approvability issues, enabling BLA resubmission.¹

The FDA has set a goal date of December 28, 2024, for cosibelimab under the Prescription Drug User Fee Act (PDUFA).

“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 of Checkpoint Therapeutics, stated in a news release. “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 suffering from CSCC.”

Data from the CSCC cohort of a registration-enabling phase 1 trial (NCT03212404) supported the BLA resubmission. At a median follow-up of 15.4 months (range, 0.4-40.5), cosibelimab generated an objective response rate (ORR) of 47.4% (95% CI, 36.0%-59.1%) by independent central review and by RECIST 1.1 criteria in patients with metastatic CSCC (n = 78); this comprised a complete response rate of 7.7%, and a partial response rate of 39.7%. Stable disease and progressive disease rates were 15.4% and 26.9%, respectively, with 10.3% of patients not evaluable for response.³

Additionally, the median duration of response (DOR) was not reached (range, 1.4+ to 34.1+ months), and 73.0% of patients displayed ongoing responses at data cutoff. The estimated 6- and 12-month DOR rates were 88.9% (95% CI, 73.1%-95.7%) and 73.0% (95% CI, 54.2%-85.0%), respectively.

This first-in-human, open-label, multicenter, dose-escalation trial assessed cosibelimab, a PD-L1 antibody, in patients with recurrent or metastatic cancers. Eligibility criteria included histologically confirmed unresectable or metastatic CSCC not amenable to local therapy, an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST 1.1 criteria, and adequate hematological, hepatic, and renal function.⁴

Patients who received prior treatment with anti–PD-1, –PD-L1, –PD-L2, –CD137, or –CTLA-4 antibodies; chemotherapy, biological cancer therapy, or TKI therapy within 4 weeks prior to the first dose; had active or a history of interstitial lung disease or pneumonitis requiring steroids; and had active, suspected, or a history of autoimmune disease were ineligible for enrollment.

In the CSCC cohort, eligible patients were treated with 800 mg of intravenous cosibelimab once every 2 weeks. The trial's primary end point was ORR, with secondary end points including DOR and safety.

Regarding safety, 11.5% of patients discontinued treatment with cosibelimab due to adverse effects (AEs), 2.6% of whom discontinued treatment due to treatment-related AEs (TRAEs).

Any-grade treatment-emergent AEs (TEAEs) occurred in 97.4% of patients, with 52.6% experiencing grade 3 or higher TEAEs. Grade 3 TRAEs were reported in 10.3% of patients, but no grade 4 or 5 TRAEs were observed. The most common TEAEs reported in more than 15% of patients included fatigue (any-grade, 26.9%; grade ≥3, 2.6%), rash (16.7%; 1.3%), and anemia (15.4%; 6.4%).

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. July 25, 2024. Accessed July 25, 2024. https://ir.checkpointtx.com/news-events/press-releases/detail/122/checkpoint-therapeutics-announces-fda-acceptance-of-bla
2. Checkpoint Therapeutics announces biologics license application resubmission for cosibelimab. News release. Checkpoint Therapeutics. July 2, 2024. Accessed July 25, 2024. https://ir.checkpointtx.com/news-events/press-releases/detail/119/checkpoint-therapeutics-announces-biologics-license
3. 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
4. Phase 1 study of CK-301 (cosibelimab) as a single agent in subjects with advanced cancers. ClinicalTrials.gov. Updated August 29, 2023. Accessed July 25, 2024. https://clinicaltrials.gov/study/NCT03212404