Dr Chandra on the Label Update for Cosibelimab in Cutaneous Squamous Cell Carcinoma

“Cosibelimab-ipdl [Unloxcyt] is the newest drug that [has] been FDA approved. It’s an anti–PD-L1 antibody, and it also has a second or a dual mechanism of action with an antibody dependent cellular toxicity. How much that mechanism of action is going to play a role in cancer cell killing is a bit unclear, but that is what separates cosibelimab from, for example, cemiplimab-rwlc [Libtayo], which is an anti–PD-1 antibody, or pembrolizumab [Keytruda], another anti–PD-1 antibody.”

Sunandana Chandra, MD, an associate professor of medicine (hematology and oncology) at the Feinberg School of Medicine at Northwestern Medicine, discussed the current systemic treatment landscape for patients with unresectable, locally advanced, or metastatic cutaneous squamous cell carcinoma (CSCC), underscoring the central role of PD-1–axis inhibition in this setting.

At present, the backbone of therapy for advanced CSCC consists of immune checkpoint inhibitors targeting the PD-1 pathway, Chandra explained. These agents function by releasing inhibitory signals on T cells, thereby enhancing the patient’s endogenous immune response against tumor cells. Among the most recently FDA-approved options is cosibelimab, an anti–PD-L1 antibody that gained a label update to the prescribing information in this disease setting in November 2025. In addition to PD-L1 blockade, cosibelimab is designed with a dual mechanism that includes antibody-dependent cellular cytotoxicity (ADCC). Although the precise contribution of ADCC to its overall antitumor activity remains to be fully elucidated, this feature differentiates cosibelimab mechanistically from PD-1–directed antibodies, Chandra noted.

For example, cemiplimab and pembrolizumab are both monoclonal antibodies that directly target PD-1 rather than its ligand. Despite these mechanistic distinctions, all 3 agents ultimately disrupt signaling along the PD-1 axis, enabling immune-mediated tumor cell killing. Clinically, this class of therapies has transformed outcomes in advanced CSCC, offering durable responses in a disease historically associated with limited systemic options, Chandra said.

Beyond PD-1–axis inhibitors, additional therapeutic strategies remain relevant in select clinical scenarios. Cetuximab (Erbitux), an EGFR-directed monoclonal antibody, may be considered, particularly for patients who are not candidates for immunotherapy or who experience disease progression, Chandra stated. Cytotoxic chemotherapy also retains a role, although its durability of benefit is generally less favorable compared with immunotherapy. Moreover, radiation therapy, though not a systemic modality, continues to serve as an important treatment option, either for local disease control, palliation, or in combination with systemic approaches in carefully selected patients, Chandra added.

Taken together, the therapeutic armamentarium for advanced CSCC reflects a shift toward immune-based strategies centered on PD-1 pathway inhibition, with emerging agents such as cosibelimab further refining this approach. Ongoing clinical experience will help clarify the relative contributions of distinct mechanisms within this class and inform optimal sequencing and patient selection strategies, Chandra concluded.