News|Articles|October 22, 2026

Cosibelimab-ipdl Gets NCCN Category 2A Nod for Locally Advanced CSCC

Cosibelimab-ipdl is now an NCCN Category 2A option for locally advanced CSCC in patients ineligible for curative surgery or radiation.

Cosibelimab-ipdl (Unloxcyt) is now a Category 2A recommended option in the updated National Comprehensive Cancer Network (NCCN) Guidelines for patients with locally advanced cutaneous squamous cell carcinoma (laCSCC) who are not candidates for curative surgery or curative radiation, Sun Pharma announced.¹ The update adds to the Category 2A designation the PD-L1–blocking antibody received in 2025 for metastatic CSCC (mCSCC), giving it guideline support in both advanced CSCC settings for which it is FDA approved.

The designation has practical weight beyond the guideline itself. NCCN recommendations inform payer coverage policies, prior-authorization criteria, institutional formularies, and clinical pathways.¹

Pivotal Trial Results: Response, Durability, and Safety

The evidence submitted to NCCN came from the pivotal registration study, in which 55% of patients with laCSCC achieved an objective response, including 26% with a complete response, according to the company.¹ At a median follow-up of 24.1 months, median duration of response (DOR) had not been reached (range, 8.3 to 31.3+ months).

Long-term results published in the Journal of the American Academy of Dermatology add further detail.² In the laCSCC cohort (n = 31), the objective response rate (ORR) was 54.8%, the complete response rate was 25.8%, and the estimated 24-month DOR rate was 80.2%. In the mCSCC cohort (n = 78), with a median follow-up of 29.3 months, ORR was 50.0%, the complete response rate was 12.8%, and the estimated 24-month DOR rate was 72.1%. Investigators reported that complete response rates increased with longer follow-up. The study was funded by Checkpoint Therapeutics, and several authors disclosed ties to the company.⁶

On safety, Sun Pharma reports that fewer than 1% of patients had a grade 3 to 5 immune-mediated adverse reaction (imAR), with no grade 4 or 5 imARs.¹ The JAAD analysis reported an overall immune-related adverse event rate of 27.6%, including 3.6% grade 3 events and none of grade 4 or higher.² The most common adverse reactions (≥10%) were fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.¹

“This guideline update reflects the strength of the published evidence supporting the use of Unloxcyt as first line treatment for laCSCC. In the pivotal study, patients experienced durable and clinically meaningful responses,” Francis Worden, MD, clinical professor of internal medicine at the University of Michigan Rogel Cancer Center, an NCCN member institution, said in a press statement.¹

“Unloxcyt 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,” Worden added.

Study Design and Mechanism

CK-301-101 (NCT03212404) was a multicenter, multicohort, open-label phase 1 trial that enrolled 109 patients across its pivotal mCSCC and laCSCC cohorts.²^,³ Patients received cosibelimab 800 mg intravenously every 2 weeks (both cohorts) or 1200 mg every 3 weeks (mCSCC cohort). ORR was the primary end point; DOR and safety were secondary end points. Key exclusions included active or suspected autoimmune disease, prior anti–PD-1/PD-L1 or other checkpoint inhibitor therapy, allogeneic transplant within 6 months, uncontrolled or significant cardiovascular disease, ECOG performance status of 2, and HIV, hepatitis B, or hepatitis C infection.³

Cosibelimab is the first and only FDA-approved PD-L1–blocking antibody for advanced CSCC; previously approved checkpoint inhibitors in this setting target PD-1.¹^,⁴ It is an unmodified immunoglobulin G1 antibody with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity (ADCC).⁴

“These clinical outcomes may be explained by the mechanism of action that restores adaptive immunity, engages innate immunity through antibody-dependent cellular cytotoxicity (ADCC), and preserves PD-L2 signaling that may be linked to the presence of some immune tolerance in non-tumor tissues,” Worden said.¹

What’s Next for Cosibelimab-ipdl?

The FDA approved cosibelimab-ipdl in December 2024 for adults with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation, and it launched commercially in the US in early 2026.³^,⁵ The recommended dosage is 1200 mg as an intravenous infusion over 60 minutes every 3 weeks.¹

An estimated 40,000 US patients each year progress to advanced CSCC, resulting in nearly 15,000 deaths, according to Sun Pharma.¹ The company expects the NCCN listing to affect how readily these patients can access treatment.

“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. NCCN recognition helps ensure that appropriate patients can receive this treatment up front without unnecessary access barriers,” Mark Gimbert, senior vice president, head of market and patient access, North America, Sun Pharma, said in a press statement.¹

References