The FDA has granted approval to Checkpoint Therapeutics' Unloxcyt (cosibelimab-ipdl) for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC) who are not candidates for curative surgery or radiation. This marks a significant advancement in treatment options for this patient population.
The approval is based on data from the phase 1 Study CK-301-101 (NCT03212404), a multicenter, multicohort, open-label trial. The study enrolled 109 patients with metastatic or locally advanced cSCC who were ineligible for surgery or radiation. Key exclusion criteria included active autoimmune disease, prior allogeneic transplant, previous anti-PD-1/PD-L1 therapy, uncontrolled cardiovascular disease, or certain infections.
Efficacy and Safety
In the study, patients received cosibelimab at 800 mg every two weeks until disease progression or intolerable toxicity. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) as assessed by an independent central review committee. For locally advanced cSCC patients with externally visible target lesions not assessable by radiologic imaging, ORR was determined via digital photography.
The ORR was 47% (95% CI: 36%, 59%) for the 78 patients with metastatic cSCC, with 8% achieving a complete response and 40% a partial response. The median DOR was not reached (range: 1.4+ to 34.1+ months). Among the 31 patients with locally advanced cSCC, the ORR was 48% (95% CI: 30%, 67%), with 10% achieving a complete response and 39% a partial response. The median DOR was 17.7 months (range: 3.7+ to 17.7 months).
The most common adverse reactions (≥10%) were fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection. Serious adverse events occurred in 31% of patients, with 8% discontinuing treatment due to adverse events.
Dosing and Administration
The recommended dose of Unloxcyt is 1,200 mg administered as an intravenous infusion over 60 minutes every three weeks until disease progression or unacceptable toxicity.
Clinical Significance
Cutaneous squamous cell carcinoma is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1.8 million cases. While most cases are localized and amenable to curative resection, approximately 40,000 cases become advanced each year, resulting in an estimated 15,000 deaths.
"cSCC remains a disease with a significant need for more effective and tolerable treatment options, particularly for patients with concomitant hematological malignancies, solid organ transplant recipients, or a history of autoimmune disorders," stated Emily Ruiz, M.D., M.P.H., Academic Director of the Mohs and Dermatologic Surgery Center at Brigham and Women's Hospital, Director of the High-Risk Skin Cancer Clinic at Dana Farber Cancer Center, and Associate Professor of Dermatology at Harvard Medical School. "UNLOXCYT is the first FDA-approved PD-L1–blocking antibody to demonstrate clinically meaningful objective response rates with durable responses in advanced cSCC."
Unloxcyt's approval provides a new immunotherapy option for U.S. oncologists in treating advanced cSCC, particularly for patients who are not candidates for surgery or radiation.
