Updated Cosibelimab Label Reflects Long-Term Data in Advanced CSCC

The FDA approved a label update to the prescribing information for cosibelimab-ipdl (Unloxcyt) to include long-term data from the phase 1 CK-301-101 trial (NCT03212404), which evaluated the agent in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC).¹

In December 2024, the FDA approved cosibelimab for the treatment of adult patients with locally advanced or metastatic CSCC who are not candidates for curative surgery or curative radiation, based on shorter-term data from CK-301-101.² Data supporting the 2024 approval showed that patients with metastatic CSCC (n = 78) experienced an objective response rate (ORR) of 47% (95% CI, 36%-59%) per independent central review (ICR); those with locally advanced CSCC (n = 31) achieved an ORR of 48% (95% CI, 30%-67%).^2,3 The median durations of response (DORs) for these respective patient populations were not reached (NR; range, 1.4+ to 34.1+) and 17.7 months (range, 3.7+ to 17.7).

The updated prescribing information for cosibelimab demonstrated that at a median follow-up of 29.3 months for patients with metastatic CSCC, the ORR was 50% (95% CI, 38%-62%), comprising a complete response (CR) rate of 13% and a partial response (PR) rate of 37%.³ In patients with locally advanced CSCC, the ORR was 55% (95% CI, 36%-73%) at a median follow-up of 24.1 months, including a CR rate of 26% and a PR rate of 29%.

The median DOR was NR (range, 1.4+ to 45.3+) in the metastatic CSCC cohort, where 85% of responders achieved a DOR of at least 6 months and 67% remained in response for at least 12 months. In the locally advanced CSCC group, the median DOR was also NR (range, 8.3 to 31.3+); all responders had a DOR that persisted for at least 6 months, and 88% remained in response for at least 12 months.

Following the label update, Sun Pharmaceutical Industries intends for the commercial launch of cosibelimab to occur in early 2026.¹

“The longer-term results confirm that [cosibelimab] represents an advancement in the available treatment options for people living with advanced CSCC," Richard Ascroft, chief executive officer of Sun Pharma North America, stated in a news release. "As a company committed to addressing the unmet needs of the patient communities we support, these pivotal data highlight that more patients responded and maintained their responses to [cosibelimab] for longer than observed in the primary analysis. The updated label reinforces [cosibelimab] as an evolution in checkpoint inhibition.”

How was the CK-301-101 trial designed to evaluate cosibelimab in advanced CSCC?

The first-in-human, open-label, multicenter, dose-escalation trial evaluated cosibelimab in patients at least 18 years of age with select recurrent or metastatic cancers, including CSCC.⁴ To enroll, patients with CSCC needed to have histologically confirmed unresectable or metastatic disease that was not amenable to local therapy. Irrespective of tumor type, all patients needed to have at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, an estimated life expectancy of at least 3 months, and adequate hematological, hepatic, and renal function.

Investigators excluded patients who received prior treatment with any anti–PD-1, anti–PD-L1, anti–PD-L2, anti-CD137, or anti–CTLA-4 antibodies, or any other agent targeting T-cell co-stimulation or immune checkpoint pathways.

Patients with advanced CSCC received cosibelimab at 800 mg every 2 weeks, with treatment continuing until disease progression or unacceptable toxicity.³

ICR-assessed ORR and DOR per RECIST 1.1 criteria served as the primary efficacy measurements for patients with CSCC.

What has been reported regarding the safety of cosibelimab in advanced CSCC?

During CK-301-101, 141 patients with advanced CSCC received cosibelimab at 800 mg every 2 weeks (n = 115) or 1200 mg every 3 weeks (n = 26), and the median duration of exposure to the agent was 36 weeks (range, 2 weeks to 3.7 years).

The most common adverse effects (AEs) reported in at least 10% of patients in the overall CSCC population included fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection. Serious AEs occurred in 31% of patients, with the most common including sepsis (2.8%), pneumonia (2.8%), and pyrexia (2.1%).

AEs led to permanent discontinuation of cosibelimab in 8% of patients with CSCC; AEs that led to treatment discontinuation (n = 1 each) comprised COVID-19, COVID-19 pneumonia, sepsis, ulcerative keratitis, tumor thrombosis, axillary pain, paresthesia, cholestasis, hepatic cytolysis, wound hemorrhage, neck pain, pemphigoid, and eye pain. Furthermore, AEs led to dose interruptions in 36% of patients; COVID-19 (2%) was the only AE leading to dose interruptions in at least 2% of patients.

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. November 25, 2025. Accessed December 2, 2025. https://sunpharma.com/wp-content/uploads/2025/11/UNLOXCYT-sBLA-Press-Release_FINAL.pdf
2. FDA approves cosibelimab-ipdl for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. December 13, 2024. Accessed December 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cosibelimab-ipdl-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma
3. Unloxcyt. Prescribing information. Checkpoint Therapeutics; 2024. Accessed December 2, 2025. https://unloxcyt.com/final-uspi_-SUN-11-2025.pdf
4. Phase 1 study of CK-301 (cosibelimab) as a single agent in subjects with advanced cancers. ClinicalTrials.gov. Updated February 3, 2025. https://clinicaltrials.gov/study/NCT03212404