NCCN Guidelines Upgrade Cosibelimab to Category 2A for Locally Advanced Cutaneous Squamous Cell Carcinoma

Cosibelimab-ipdl (Unloxcyt) has been elevated to a category 2A preferred option in the updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for patients with locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.¹

The new recommendation adds to the category 2A designation the PD-L1 inhibitor was assigned in 2025 for metastatic CSCC.

The update is supported by data from the locally advanced cohort of a pivotal, open-label, multicohort phase 1 Study CK-301-101 (NCT03212404). At a median follow-up of 24.1 months, evaluable patients (n = 31) achieved an objective response rate (ORR) of 54.8%, including a complete response (CR) rate of 25.8%.^1,2 The median duration of response (DOR) was not reached (range, 8.3 to 31.3+), and the estimated 24-month DOR rate was 80.2%.^1,2 Long-term results from the trial were published in the Journal of the American Academy of Dermatology.²

"This [NCCN] guideline update reflects the strength of the published evidence supporting the use of Unloxcyt as first line treatment for locally advanced CSCC," Francis Worden, MD, clinical professor of internal medicine at the University of Michigan Rogel Cancer Center, stated in a news release.¹ "In the pivotal study, patients experienced durable and clinically meaningful responses."

In December 2024, the FDA approved cosibelimab for the treatment of adults with metastatic or locally advanced CSCC who are not candidates for curative surgery or radiation, based on data from Study CK-301-101.³

How was Study CK-301-101 designed?

The multicenter, multiregional phase 1 trial enrolled patients with unresectable or metastatic CSCC that was not amenable to local therapy, along with cohorts in other advanced cancers.^2,4

In the CSCC cohorts, patients received intravenous cosibelimab at 800 mg every 2 weeks; a subset of patients in the metastatic cohort received 1,200 mg every 3 weeks.²

The primary end point was ORR by independent central review per RECIST 1.1 criteria, and secondary end points included DOR and safety.^2,4

In the metastatic cohort (n = 78), at a median follow-up of 29.3 months, the ORR was 50.0% (39/78), including a CR rate of 12.8% (10/78).² The median DOR was not reached, and the estimated 24-month DOR rate was 72.1%.

What is the safety profile of cosibelimab?

Across the CSCC cohorts, the rate of immune-related adverse effects (AEs) was 27.6%, with grade 3 events occurring in 3.6% of patients and no grade 4 or 5 events.² In the initial analysis of the metastatic cohort, the most common treatment-emergent AEs reported in at least 15% of patients were fatigue (26.9%), rash (16.7%), and anemia (15.4%); no treatment-related deaths were reported.⁴

The most common adverse reactions occuring in at least 10% of patients treated with cosibelimab include fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.¹

References

1. Sun Pharma announces Unloxcyt (cosibelimab-ipdl) has received a category 2A preferred designation in the updated NCCN Guidelines for locally advanced cutaneous squamous cell carcinoma (laCSCC) patients who are not candidates for curative surgery or curative radiation. News release. Sun Pharmaceutical Industries Ltd. October 20, 2026. Accessed October 20, 2026. https://sunpharma.com/wp-content/uploads/2026/10/Sun-Pharma-Announces-UNLOXCYT%C2%AE-cosibelimab-ipdl-Has-Received-a-Category-2A-Preferred-Designation-in-the-Updated-NCCN-Guidelines-for-Locally.pdf
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. 2026;94(1):48-56. doi:10.1016/j.jaad.2025.09.009
3. FDA approves cosibelimab-ipdl for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. December 13, 2024. Accessed October 20, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cosibelimab-ipdl-metastatic-or-locally-advanced-cutaneous-squamous-cell-carcinoma
4. 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