Cosibelimab Delivers Durable Responses in Advanced CSCC

Immune checkpoint inhibition has reshaped management of advanced cutaneous squamous cell carcinoma (CSCC), particularly for patients who are not candidates for curative surgery or radiation. PD-1 inhibitors set the current standard, but questions remain about durability, complete response rates, and immune-related toxicity, especially in an older population with comorbidities.

Long-term data from the pivotal cosibelimab study now clarify where PD-L1 blockade may fit in this landscape. In the Journal of the American Academy of Dermatology, researchers report extended follow-up from a multicenter, open-label phase 1 trial of cosibelimab in metastatic CSCC (mCSCC) and locally advanced CSCC (laCSCC), with median follow-up approaching 2 years or longer in both cohorts.

Here’s a quick overview of the trial.

Study Design and Population

The efficacy population included 78 patients with mCSCC and 31 with laCSCC treated at 800 mg every 2 weeks. Patients were predominantly older than 70 years, with most previously treated with surgery or radiation but over 90% had not received prior systemic therapy. Median follow-up reached 29.3 months in mCSCC and 24.1 months in laCSCC.

The primary endpoint was objective response rate by independent central review using RECIST 1.1 and WHO criteria for externally visible lesions. Duration of response and safety were key secondary measures.

Durability Strengthens With Time

At extended follow-up, cosibelimab maintained clinically meaningful activity:

• ORR 50.0% in mCSCC, with 12.8% complete responses
• ORR 54.8% in laCSCC, with 25.8% complete responses
• Median duration of response not reached in either cohort
• Estimated 24-month duration-of-response rates 72.1% in mCSCC and 80.2% in laCSCC

Responses deepened over time, with increasing complete response rates compared with earlier analyses. Median time to response remained under 4 months, and durability extended beyond 2 years in a substantial subset. PD-L1 expression did not clearly predict benefit.

Safety in an Older Population

Across 192 treated patients in the safety population:

• Immune-related adverse events occurred in 27.6%
• Grade 3 immune-related events occurred in 3.6%
• No grade 4 or higher immune-related events were reported
• No treatment-related deaths occurred

For a population in which median age exceeds 70 years and comorbidity is common, low rates of severe immune toxicity carry practical implications. Older patients often face competing risks from frailty, cardiovascular disease, and polypharmacy. A PD-L1–directed strategy that preserves PD-L2–PD-1 interaction may contribute to a differentiated safety profile, although cross-trial comparisons should be interpreted cautiously.

Context Within the CSCC Landscape

Cemiplimab and pembrolizumab have demonstrated comparable response rates in advanced CSCC. What distinguishes cosibelimab in this dataset is the combination of sustained durability and low rates of high-grade immune toxicity over extended follow-up. Direct comparative data are lacking, but these findings position PD-L1 blockade as a reasonable alternative mechanism within the immunotherapy class.

The absence of randomization remains a central limitation. The study design precludes head-to-head comparisons, and biomarker analyses were limited. Additionally, complete responses in externally visible lesions were not pathologically confirmed in all cases. Still, the follow-up duration now approaches the time horizon clinicians use to assess meaningful durability in advanced skin cancers.

Looking Ahead in Advanced CSCC

For patients with unresectable laCSCC or mCSCC, durable tumor control with manageable toxicity may be achievable for many patients with cosibelimab.

As treatment algorithms evolve, selection among PD-1 and PD-L1 inhibitors may hinge less on efficacy differences and more on tolerability, patient comorbidity, and access considerations. Further real-world data and comparative effectiveness analyses will help clarify positioning. For now, cosibelimab expands the immunotherapy toolkit in advanced CSCC, with durability that holds at 2 years and a safety profile that appears consistent over time.

Reference:

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