Cosibelimab Receives FDA Approval for Squamous Cell Skin Cancer

On December 13, 2024, the US Food and Drug Administration (FDA) approved cosibelimab-ipdl (Unloxcyt, Checkpoint Therapeutics, Inc.), an anti-PD-L1 immunotherapy drug, for patients ineligible for curative surgery or curative radiation who have metastatic cutaneous squamous cell carcinoma (mcSCC) or locally advanced cutaneous squamous cell carcinoma (lacSCC) in adulthood.

This is the first FDA approval for cosibelimab-ipdl (Unloxcyt) immunotherapy.

Cutaneous squamous cell carcinoma (cSCC) develops through uncontrolled proliferation of squamous cells in the upper layer of the skin, the epidermis, and is a type of skin cancer. It generally occurs in sun-exposed areas and may spread into surrounding tissues or other organs if not treated early.

Other immunotherapies approved by the FDA for squamous cell skin cancer before cosibelimab-ipdl include:

1. Cemiplimab (Libtayo): On September 28, 2018, the FDA approved cemiplimab for advanced cSCC. It was the first FDA-approved immunotherapy for cSCC.

2. Pembrolizumab (Keytruda): On June 24, 2020, the FDA approved pembrolizumab for recurrent or metastatic cSCC that cannot be treated with surgery or radiotherapy.

FDA Approval Based on the CK-301-101 Study

The effectiveness of cosibelimab-ipdl was evaluated in the CK-301-101 Study . This was a multicenter, multicohort, open-label study involving 109 patients with metastatic or locally advanced disease who were ineligible for curative surgery or radiation. Patients with the following characteristics were excluded:

• Active or suspected autoimmune disease,
• Within the 6 months before treatment, receipt of an allogeneic transplant,
• Prior treatment with anti-PD-1/PD-L1 blocking antibodies or other immune checkpoint inhibitors ,
• Uncontrolled or severe cardiovascular disease,
• ECOG performance status ≥ 2,
• HIV, hepatitis B, or hepatitis C infection.

The main efficacy measures were objective response rate and duration of response . For lacSCC patients with externally visible target lesions that could not be assessed radiologically, objective response was determined using digital photography according to WHO criteria.

• In metastatic cSCC , among 78 patients, the objective response rate was 47% (95% CI: 36-59),
• In locally advanced cSCC , among 31 patients, the objective response rate was 48% (95% CI: 30-67).
• Duration of Response: Median duration of response was not reached in mcSCC (range: 1.4+ to 34.1+ months); it was 17.7 months in lacSCC (range: 3.7+ to 17.7 months).

Adverse Effects

Most common adverse effects (≥10%):

• Fatigue,
• Musculoskeletal pain,
• Rash, diarrhea, hypothyroidism, constipation,
• Nausea, headache, itching, edema,
• Local infection and urinary tract infection.

Dose and Administration

The recommended dose of cosibelimab-ipdl is

• 1200 mg by intravenous infusion over 60 minutes , once every 3 weeks . Treatment continues until disease progression or unacceptable toxicity.

This approval offers new hope to patients with mcSCC or lacSCC who are ineligible for curative treatment. Study data show that cosibelimab-ipdl provides high response rates and prolonged response durations.