NCCN Guidelines Add Cosibelimab for Locally Advanced CSCC

The National Comprehensive Cancer Network (NCCN) has added cosibelimab-ipdl (Unloxcyt) as a category 2A recommended option for patients with locally advanced cutaneous squamous cell carcinoma (laCSCC) who are not candidates for curative surgery or curative radiation.^1,2

The update extends an existing category 2A recommendation for cosibelimab in metastatic CSCC (mCSCC), which NCCN assigned in 2025. According to a news release, Sun Pharma’s submission to NCCN was based on results from the pivotal CK-301-101 trial (NCT03212404), in which 55% of patients with laCSCC had an objective response, including 26% with a complete response (CR). At a median follow-up of 24.1 months, the median duration of response (DOR) had not been reached (range, 8.3-31.3+ months).^1,3

"This guideline update reflects the strength of the published evidence supporting the use of UNLOXCYT as first line treatment for laCSCC," Francis Worden, MD, clinical professor of internal medicine at the University of Michigan Rogel Cancer Center in Ann Arbor, an NCCN member institution, stated in the news release. "In the pivotal study, patients experienced durable and clinically meaningful responses."¹

Regulatory Background

Cosibelimab is an anti–PD-L1 antibody. The FDA approved cosibelimab in December 2024 for adults with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation. The labeled dose is 1200 mg given intravenously over 60 minutes every 3 weeks. Sun Pharma described cosibelimab as the only PD-L1–blocking antibody approved by the FDA for advanced CSCC.

In the NCCN guidelines, in addition to cosibelimab, cemiplimab (Libtayo) and pembrolizumab (Keytruda) are also listed as preferred options for systemic therapy alone for locally advanced, recurrent, or metastatic disease if curative radiotherapy or surgery are not indicated, as is referral to clinical trial.²

Sun Pharma noted that NCCN recommendations shape insurer coverage decisions, prior authorization requirements, hospital formularies, and treatment pathways.¹

Supporting Data

CK-301-101 is an open-label, multicenter, multiregional trial with separate cohorts for patients with metastatic and locally advanced CSCC. Patients in the laCSCC cohort received cosibelimab 800 mg every 2 weeks, while some patients with mCSCC received 1200 mg every 3 weeks; the investigators reported that the 2 regimens produce comparable drug exposure.³

Patients in the laCSCC cohort had a mean age of 76.5 years, and most had undergone prior cancer surgery (80.6%) or radiation therapy (77.4%). Only 1 patient (3.2%) had received prior systemic therapy. Median DOR was not reached (range, 8.3-31.3+ months), and the Kaplan-Meier estimated probability of remaining in response at 24 months was 80.2%. Responses occurred regardless of tumor PD-L1 status, with an ORR of 53% among patients with PD-L1–positive tumors and 38% among those with PD-L1–negative tumors, and no statistical correlation between response and PD-L1 expression. In the mCSCC cohort (n = 78), the ORR was 50.0% (95% CI, 38.5-61.5) and the CR rate was 12.8% at a median follow-up of 29.3 months.³

Safety Findings

Among 192 patients evaluable for safety across both cohorts, 94.3% had treatment-emergent adverse events (TEAEs), most commonly fatigue (22.9%), anemia (20.3%), constipation (16.1%), and diarrhea (15.1%). Immune-related adverse events (irAEs) occurred in 27.6% of patients and were grade 3 in 3.6%; no grade 4 or higher irAEs were reported, and there were no grade 3 or higher cases of pneumonitis, colitis, hepatitis, nephritis, or endocrinopathies. TEAEs led to permanent discontinuation in 6.3% of patients. Six patients (3.1%) died of TEAEs, all considered unrelated to cosibelimab.² Sun Pharma reported in its release that fewer than 1% of patients had grade 3 to 5 immune-mediated adverse events.¹

Worden noted that the low incidence of high-grade immune-mediated adverse reactions is relevant for a population that is largely older and often has comorbidities. He also suggested that the drug's activity may relate to its mechanism of action, which he described as reactivating adaptive immune responses, recruiting innate immune effectors via antibody-dependent cellular cytotoxicity, and leaving PD-L2 signaling intact.¹ The study authors similarly noted that the rate of severe irAEs with cosibelimab was lower than rates reported with PD-1 inhibitors in this disease and proposed that preserved PD-L2 signaling may contribute.³

"The elevation of [cosibelimab] to a category 2A recommendation for patients with laCSCC marks an important milestone, validating the growing body of clinical evidence supporting [cosibelimab] and reflecting increasing confidence among oncology experts in its role as a treatment option for patients with this challenging disease," said Ahmad Naim, MD, senior vice president and North American chief medical officer at Sun Pharma, in the news release.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 Pharma. October 20, 2026. Accessed October 21, 2026. https://tinyurl.com/bdcyehh5

2. NCCN. Clinical Practice Guidelines in Oncology. Squamous cell skin cancer, version 1.2027. Accessed October 21, 2026. https://tinyurl.com/3j7xrxp7

3. 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