Cutaneous squamous cell carcinoma (CSCC) is one of the most common skin cancers, with cases ranging from easily treatable localized lesions to aggressive forms that can metastasize or become life-threatening. On December 13, 2024, the FDA approved cosibelimab-ipdl (Unloxcyt), a PD-L1 blocking antibody, offering new hope for adults with metastatic CSCC (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or radiation. This milestone marks a significant advancement in immunotherapy for skin cancers.
Background on Cutaneous Squamous Cell Carcinoma
CSCC is the second most common type of skin cancer after basal cell carcinoma. It arises from squamous cells in the outermost layer of the skin, often due to chronic sun exposure, immunosuppression, or carcinogenic factors.
Clinical Features and Risk Factors
- Early-stage CSCC: Typically presents as a scaly, red patch, wart-like growth, or open sore that may crust or bleed. Early treatment, usually surgical, is often curative.
- Advanced CSCC: May invade deeper tissues, including bone, or metastasize to distant organs such as lymph nodes or lungs.
- Risk Factors: Chronic sun exposure, immunosuppressive therapy (e.g., post-transplant), exposure to carcinogens, and a history of skin cancer.
Challenges in Advanced Disease
For patients with metastatic or locally advanced CSCC, treatment options have historically been limited:
- Surgery and radiation are often infeasible due to the extent of disease or comorbidities.
- Chemotherapy, though sometimes used, is associated with significant toxicity and modest efficacy.
FDA Approval of Cosibelimab (Unloxcyt): A New Option for Advanced CSCC
The FDA’s approval of cosibelimab-ipdl introduces a new immunotherapy option for patients with advanced CSCC, particularly those who cannot undergo curative surgery or radiation. Cosibelimab is a PD-L1 blocking antibody that enhances the immune system’s ability to recognize and attack cancer cells.
Key Results from the CK-301-101 Study
The approval was based on results from a multicenter, multicohort, open-label trial that included 109 patients with metastatic or locally advanced CSCC.
- Objective Response Rate (ORR):
- 47% (95% CI: 36–59) for metastatic CSCC.
- 48% (95% CI: 30–67) for locally advanced CSCC.
- Duration of Response (DOR):
- Not reached for metastatic CSCC (range: 1.4+, 34.1+ months).
- 17.7 months for locally advanced CSCC (range: 3.7+, 17.7 months).
These results highlight cosibelimab’s ability to achieve durable responses in a challenging patient population.
Safety Profile
Cosibelimab was generally well-tolerated, with a manageable safety profile consistent with other immune checkpoint inhibitors.
- Common Adverse Reactions (≥10%):
Fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, nausea, and infections were among the most frequently reported side effects. - Recommended Dosage:
1,200 mg administered intravenously over 60 minutes every three weeks until disease progression or unacceptable toxicity.
What This Approval Means for Patients
For patients with advanced CSCC who have few viable treatment options, cosibelimab represents a new standard of care:
- Expanded Options: Provides an immunotherapy approach for those who cannot undergo curative procedures.
- Durable Responses: With nearly half of patients responding to treatment, cosibelimab offers hope for prolonged disease control.
- Improved Quality of Life: Compared to traditional treatments, immunotherapy often has a more tolerable safety profile.
Looking Ahead
The approval of cosibelimab underscores the growing role of immunotherapy in managing skin cancers. For oncologists and dermatologists, this is a reminder to consider genetic and immunological markers when planning treatments for advanced CSCC. For patients, it represents a step forward in improving survival and quality of life.
As more studies evaluate cosibelimab and its potential combinations with other therapies, the landscape of skin cancer treatment will continue to evolve. This approval is a promising addition to the arsenal of therapies that can help patients face even the most aggressive forms of CSCC.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.