Cosibelimab Now NCCN Category 2A in Locally Advanced Cutaneous Squamous Cell Carcinoma

Cosibelimab-ipdl (Unloxcyt) has been elevated to a category 2A recommended option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for patients with locally advanced cutaneous squamous cell carcinoma (laCSCC) who are not candidates for curative surgery or curative radiation, according to a news release from Sun Pharma.¹

According to Version 1.2027 of the NCCN Guidelines for Squamous Cell Skin Cancer, dated October 8, 2026, cosibelimab moved from the “other recommended” category to the “preferred” category of options for systemic therapy alone in patients for whom curative radiotherapy (RT) or surgery is not feasible for locally advanced, recurrent, or metastatic disease. The category of preference for the locally advanced option changed from 2B to 2A.² The update builds on the category 2A designation for patients with metastatic CSCC (mCSCC) that was assigned to the agent in 2025.¹

“The NCCN Guidelines play an important role in helping physicians evaluate appropriate treatment options for patients across different disease settings,” Ahmad Naim, MD, senior vice president and North American chief medical officer of Sun Pharma, said in the news release. “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.”

Based on results from a pivotal registrational study, in which 55% of patients had an objective response rate (ORR) and supports this change with the NCCN. Additionally, 26% of patients who achieved a complete response. At a median follow-up of 24.1 months, the median duration of response (DOR) had not been reached (range, 8.3 to 31.3+ months). Fewer than 1% of patients experienced a grade 3 to 5 immune-mediated adverse reaction (imAR), and no grade 4 or 5 imARs were reported.¹

“This guideline update reflects the strength of the published evidence supporting the use of [cosibelimab] as first line treatment for laCSCC,” said Francis Worden, MD, clinical professor of internal medicine at the University of Michigan Rogel Cancer Center, an NCCN member institution. “In the pivotal study, patients experienced durable and clinically meaningful responses. [Cosibelimab] also demonstrated a low incidence of high-grade imARs—an important consideration when selecting immune checkpoint inhibitor therapy for a patient population that is mainly elderly and is often afflicted with other health issues.”

Regulatory Background and Supporting Data

The FDA approved cosibelimab on December 13, 2024, for adults with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation.³ The approval was supported by findings from the multicenter, multicohort, open-label CK-301-101 study (NCT03212404), which included 109 patients.⁴ Patients with active or suspected autoimmune disease, prior anti–PD-1/PD-L1 or other checkpoint inhibitor therapy, uncontrolled significant cardiovascular disease, an ECOG performance status of 2 or higher, or HIV, hepatitis B, or hepatitis C were excluded.

Per independent central review, the ORR was 47% (95% CI, 36%-59%) among 78 patients with mCSCC, with a median DOR that was not reached (range, 1.4+ to 34.1+ months). Among 31 patients with laCSCC, the ORR was 48% (95% CI, 30%-67%), with a median DOR of 17.7 months (range, 3.7+ to 17.7).³

Primary results from the mCSCC cohort were published in the Journal for ImmunoTherapy of Cancer. In that analysis, the 78 enrolled patients had a median age of 71.6 years (range, 37-91). The confirmed ORR was 47.4% (95% CI, 36.0%-59.1%), including complete responses in 7.7% of patients and partial responses in 39.7%. At a median follow-up of 15.4 months, responses were ongoing in 73.0% of responders.⁴

Regarding safety in that cohort, treatment-related grade 3 events occurred in 10.3% of patients, with no treatment-related grade 4 or 5 events. Immune-related adverse events (AEs) occurred in 23.1% of patients, including grade 3 events in 2.6%. The most common treatment-emergent AEs were fatigue (26.9%), rash (16.7%), and anemia (15.4%). Treatment-emergent AEs led to discontinuation in 11.5% of patients, including 2.6% considered related to cosibelimab.⁴

Cosibelimab is a high-affinity, fully human monoclonal antibody that binds PD-L1, blocking its interaction with PD-1 to reactivate T cells. Its Fc domain can also induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against tumor cells.⁴

Guideline Context and Patient Access

In the updated NCCN Guidelines, cosibelimab joins cemiplimab-rwlc (Libtayo), pembrolizumab (Keytruda), and clinical trial enrollment as preferred options for systemic therapy alone in this setting. For patients with laCSCC who are not candidates for curative surgery or curative RT, the guidelines recommend multidisciplinary consultation to discuss systemic therapy alone. The guidelines also note that, in solid organ transplant recipients, the potential benefit of immune checkpoint inhibitor therapy must be weighed against a significant risk of organ rejection.²

“For patients with laCSCC—many of whom are older, medically complex, and vulnerable to treatment-related complications—access to a therapy that offers durable responses together with a low rate of high-grade imARs is especially important,” said Mark Gimbert, senior vice president and head of Market and Patient Access, North America, at Sun Pharma. “NCCN recognition helps ensure that appropriate patients can receive this treatment up front without unnecessary access barriers.”

The recommended dose of cosibelimab is 1200 mg as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.^1,3 Warnings and precautions include severe and fatal imARs, which can affect any organ system, as well as infusion-related reactions and embryo-fetal toxicity. Liver enzymes, creatinine, and thyroid function should be evaluated at baseline and periodically during treatment. The most common adverse reactions, occurring in at least 10% of patients, included 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 Pharma. October 20, 2026. Accessed October 21, 2026. https://tinyurl.com/wwzk2jh9
2. NCCN. Clinical Practice Guidelines in Oncology. Squamous cell skin cancer, version 1.2027. Accessed October 21, 2026. https://tinyurl.com/4bdns5ff
3. FDA approves cosibelimab-ipdl for metastatic or locally advanced cutaneous squamous cell carcinoma. FDA. December 13, 2024. Accessed October 21, 2026. https://tinyurl.com/42759enz
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