FDA Expands Cosibelimab-ipdl Label to Include Long-Term Data From the CK-301-101 Trial

The FDA expanded the label indication of cosibelimab-ipdl (Unloxcyt; Sun Pharmaceutical Industries) for adults with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC (aCSCC) to include long-term follow-up data from the CK-301-101 trial (NCT03212404), showing that about 50% of patients in the trial achieved the primary end point of objective response rate (ORR).^1,2

"The longer-term results confirm that [cosibelimab-ipdl] represents an advancement in the available treatment options for people living with aCSCC," Richard Ascroft, CEO, Sun Pharma North America, said in a press release. "...[T]hese pivotal data highlight that more patients responded and maintained their responses to [cosibelimab-ipdl] for longer than observed in the primary analysis. The updated label reinforces [cosibelimab-ipdl] as an evolution in checkpoint inhibition."²

Cosibelimab-ipdl is a PD-L1 inhibitor that activates innate and adaptive immunity by blocking PD-L1 interactions with PD-1 and B7-1 receptors. Cosibelimab-ipdl activates the innate immune system through its functional Fc domain, which engages natural killer (NK) cells to trigger antibody-dependent cell-mediated cytotoxicity.^2,3

In addition, cosibelimab-ipdl does not target PD-L2, a feature that may help maintain immune tolerance in healthy tissues like the lung and liver, potentially reducing off-target effects and immune-mediated adverse reactions.²

Cosibelimab-ipdl received initial FDA approval in 2024 following positive results from the CK-301-101 trial for treatment of adults with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation.^2,3

CK-301-101 multicenter, multicohort, open-label study investigating cosibelimab-ipdl for the treatment of adults with metastatic CSCC (mCSCC) or locally aCSCC who are not candidates for curative surgery or curative radiation. They evaluated a total of 109 patients (31 with laCSCC; 78 with mCSCC) who were treated with 800 mg of cosibelimab intravenously every 2 weeks.^2,3

The primary end point of the study was ORR and a key secondary end point of duration of response (DOR).^2,3

The long-term data show that patients receiving cosibelimab-ipdl achieved durable responses, with about 50% of the trial population achieving the primary end point of ORR. Although the duration of response was not reached in either trial group, the investigators reported a median time to response of 1.9 months (range: 1.6-16.9) and 3.6 months (range: 1.7-10.1) in patients with mCSCC and laCSCC, respectively. Fourteen percent of mCSCC patients and 32% of laCSCC patients achieved stable disease.²

The safety profile was favorable, with the most common adverse effects (AEs) being fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection (≥ 10%).²

In the trial, 53 patients (24%) experienced immune-mediated AEs (any grade), with high-grade events occurring infrequently. Only 2 patients (0.9%) developed high-grade immune-mediated adverse reactions, both of which were grade 3 dermatologic reactions. No treatment-related deaths were reported.²

"While there have been advances in aCSCC treatment, there still 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 are dealing with significant comorbidities," Emily Ruiz, MD, MPH, Associate Professor of Dermatology, Harvard Medical School, Academic Director of the Micrographic Surgery Center at Brigham and Women's Hospital, co-founder of Skin Cancer Champions, and primary author on the long-term analysis publication, said in a press release.²

"For many aCSCC patients who are over the age of 65 and dealing with comorbidities, [cosibelimab-ipdl] provides an important, new treatment option that balances both efficacy and tolerability."²

REFERENCES

1. 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://clinicaltrials.gov/study/NCT03212404#study-plan

2. 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). PR Newswire. November 25, 2025. Accessed December 1, 2025. https://www.prnewswire.com/news-releases/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-302626366.html

3. McGovern G. FDA Approves Cosibelimab-Ipdl for Adult Patients with mCSCC or laCSCC. Pharmacy Times. December 16, 2024. Accessed December 1, 2025. https://www.pharmacytimes.com/view/fda-approves-cosibelimab-ipdl-for-adult-patients-with-mcscc-or-lacscc