BLA Resubmitted for Cosibelimab in Advanced Squamous Cell Carcinoma

The resubmitted BLA aims to address all insufficiencies that the FDA highlighted in a complete response letter for cosibelimab in December 2023.

Developers have resubmitted a biologics license application (BLA) seeking approval for the investigational anti–PD-L1 agent cosibelimab (CK-301) as a treatment for those with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) not eligible to receive curative surgery or radiotherapy, according to a press release from Checkpoint Therapeutics, Inc.¹

The resubmitted BLA aims to address all insufficiencies that the FDA highlighted in a complete response letter for cosibelimab in December 2023.² At the time, the regulatory agency identified issues for approval following a multi-sponsor inspection of a third-party manufacturing organization. The letter did not describe any problems with the clinical data, safety, or labeling associated with cosibelimab.

Supporting data for the resubmitted BLA came from a phase 1 study (NCT03212404) assessing the efficacy and safety of cosibelimab as a treatment for patients with metastatic CSCC.

According to updated findings published in the Journal for ImmunoTherapy of Cancer, treatment with cosibelimab produced an overall response rate (ORR) of 47.4% (95% CI, 36.0%-59.1%) across the intent-to-treat population, which included partial responses (PRs) in 31 patients and complete responses (CRs) in 6.³ Additionally, the median time to response was 1.9 months (range, 1.6-6.6). The median duration of response (DOR) was not reached (range, 1.4+ to 34.1+ months), and ongoing responses were reported in 73.0% of patients.

Common treatment-emergent adverse effects (TEAEs) included fatigue (26.9%), rash (16.7%), and anemia (11.5%). Additionally, the most frequent grade 3 or higher toxicity was anemia (6.4%). Investigators reported that 3.8% of patients died due to AEs, although these toxicities were unrelated to study treatment.

“…Our data from this pivotal study of patients with [metastatic] CSCC from an open-label, multicenter, multiregional, multicohort, phase 1 trial suggest that cosibelimab is associated with robust antitumor activity, durable responses, and a well-tolerated profile,” the study authors wrote. “Long-term follow-up of the [patients] is ongoing to continue the characterization of the safety and efficacy profile of cosibelimab.”

In this phase 1 trial, patients with metastatic CSCC were assigned to receive cosibelimab at 800 mg intravenously every 2 weeks.

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

Patients 18 years and older with histologically confirmed unresectable or metastatic CSCC not amenable to local therapy were eligible for enrollment on the trial.⁴ Additional eligibility criteria included having an ECOG performance status of 0 or 1, an estimated life expectancy of 3 or more months, and at least 1 measurable lesion per RECIST v1.1 guideline. Having adequate hematologic, hepatic, and renal function was another requirement for study entry.

Those with prior severe hypersensitivity to other monoclonal antibodies or prior treatment with antibodies targeting PD-1, PD-L1, PD-L2, CD137, or CTLA-4 were ineligible for enrollment on the trial. Having active or prior interstitial lung disease or active or suspected autoimmune disease was also grounds for exclusion from the trial.

“We are excited to see the substantial increases in the rate of patients experiencing a complete response of their cSCC tumors with further cosibelimab treatment in both our locally advanced and metastatic pivotal trials,” James Oliviero, president and chief executive officer at Checkpoint Therapeutics, said in a press release on prior findings on cosibelimab in locally advanced and metastatic CSCC in July 2023.⁵

Developers originally submitted the BLA for cosibelimab as a treatment for CSCC in January 2023.⁶

References

1. 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
2. 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 2, 2024. https://tinyurl.com/5yewpx4b
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. Accessed July 2, 2024. https://tinyurl.com/5dfpxrvb
5. Checkpoint Therapeutics announces cosibelimab longer-term results demonstrating substantial increases in complete response rates in advanced cutaneous squamous cell carcinoma. News release. Checkpoint Therapeutics, Inc. July 27, 2023. Accessed July 2, 2024. https://shorturl.at/cgrEH
6. 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 2, 2024. yhoo.it/3GqykPg