FDA Approves Updated Cosibelimab Label in Cutaneous Squamous Cell Carcinoma

The FDA has approved an updated label for cosibelimab-ipdl (Unloxcyt) as a treatment for adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are ineligible to receive curative surgery or radiation, according to a press release from the developer, Sun Pharmaceutical Industries Limited.¹

The updated labeling is based on updated findings from the phase 1 CK-301-101 trial (NCT03212404), in which investigators assessed treatment with cosibelimab among 109 patients with CSCC, including 31 and 78, respectively, with locally advanced and metastatic disease. These findings were published in the Journal of the American Academy of Dermatology.²

With a median follow-up of 29.3 months (95% CI, 25.3-34.8) in the metastatic CSCC cohort and 24.1 months (95% CI, 22.6-26.9) in the locally advanced CSCC cohort, the objective response rate (ORR) was 50.0% (95% CI, 38.5%-61.5%) and 54.8% (95% CI, 36.0%-72.7%) in each respective group. Additionally, complete responses (CRs) occurred in 12.8% and 25.8% of each group, and 37.2% and 29.0% experienced partial responses (PRs).

Data showed that median duration of response (DOR) was not reached (NR; range, 1.4-45.3+) in the metastatic disease cohort and NR (range, 8.3-31.3+) in the locally advanced disease cohort. Per Kaplan-Meier analysis, the estimated probability of response in each arm was 89.5% (95% CI, 74.3%-95.9%) and 100% (95% CI, not evaluable [NE]-NE) at 6 months, 75.4% (95% CI, 57.9%-86.4%) and 88.2% (95% CI, 60.6%-96.9%) at 12 months, and 72.1% (95% CI, 54.1%-84.0%) and 80.2% (95% CI, 49.6%-93.3%) at 24 months.

Overall, 94.3% of patients experienced treatment-emergent adverse effects (TEAEs) of any grade, and 45.3% had grade 3 or higher toxicities. The most common any-grade TEAEs included fatigue (22.9%), anemia (20.3%), constipation (16.1%), diarrhea (15.1%), and pruritus (13.5%). TEAEs resulted in treatment discontinuation for 6.3% of patients, and 3.1% died due to TEAEs.

“While there have been advances in [advanced] CSCC treatment, there remains a significant unmet need for therapies that provide durable, long-term efficacy with acceptable tolerability. This is especially important in this aging population who [have] significant comorbidities,” lead study author Emily S. Ruiz, MD, MPH, associate professor of Dermatology at Harvard Medical School, academic director of the Micrographic Surgery Center at Brigham and Women’s Hospital, and co-founder of Skin Cancer Champions, stated in the press release.¹ “For many [patients with advanced] CSCC who are over the age of 65…with comorbidities, [cosibelimab] provides an important, new treatment option that balances both efficacy and tolerability.”

In the ongoing, open-label, multicenter, multicohort CK-301-101 trial, patients were assigned to receive cosibelimab intravenously at 800 mg every 2 weeks or 1200 mg every 3 weeks.

The trial’s primary end point was ORR per independent central review using RECIST v1.1 criteria. Secondary end points included DOR and incidence and severity of TEAEs per CTCAE v5.0 criteria.

Patients 18 years and older with histologically confirmed unresectable or metastatic CSCC not amenable to local therapy; adequate hematologic, hepatic, and renal function; and at least 1 measurable lesion per RECIST v1.1 guidelines were eligible for enrollment on the trial.³ Investigators also assessed cosibelimab among patients with other types of solid tumors, including but not limited to non–small cell lung cancer, colorectal cancer, endometrial carcinoma, malignant pleural or peritoneal mesothelioma, stage III or metastatic melanoma, and renal cell carcinoma.

The FDA originally approved cosibelimab for patients with locally advanced or metastatic CSCC in December 2024.⁴ The original approval was based on earlier findings from the CK-301-101 trial.

References

1. FDA approves label update for UNLOXCYT™ (cosibelimab-ipdl) based on longer-term data that demonstrated improved clinical outcomes in advanced cutaneous squamous cell carcinoma (aCSCC). News release. Sun Pharmaceutical Industries Limited. November 25, 2025. Accessed December 1, 2025. https://tinyurl.com/yp5a5y5x
2. Ruiz ES, Muñoz-Couselo E, Montaudié H, et al. Efficacy and safety of cosibelimab in advanced cutaneous squamous cell carcinoma: results from a pivotal open-label study with a median follow-up of ≥2 years. J Am Acad Dermatol. 2025;S0190-9622(25)02791-4. doi:10.1016/j.jaad.2025.09.009.
3. Phase 1 study of CK-301 (cosibelimab) as a single agent in subjects with advanced cancers. ClinicalTrials.gov. Updated February 3, 2025. Accessed December 1, 2025. https://tinyurl.com/4dmmwvys
4. FDA approves cosibelimab-ipdl for metastatic or locally advanced cutaneous squamous cell carcinoma. News release. FDA. December 13, 2024. Accessed December 1, 2025. https://tinyurl.com/2wdtzrxa