On June 24, 2020, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda®) for patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable with surgery or radiation.
Efficacy was investigated in a multicenter, multicohort, nonrandomized, open-label trial (KEYNOTE-629; NCT03284424) that excluded patients who had previously received therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody and those with an autoimmune disease or medical condition that required immunosuppression. Patients received pembrolizumab 200 mg via IV every three weeks for a maximum of 24 months or until they experienced disease progression or unacceptable toxicity. Researchers assessed patients’ tumor status every six weeks during the first year and every nine weeks during the second year.
The major efficacy outcome measures were objective response rate (ORR) and response duration as determined by blinded, independent central review, according to response evaluation criteria in solid tumors 1.1 that was modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. ORR was 34% (95% CI = 24, 44), and median response duration was not reached (range = 2.7, 13.1+ months).
Adverse reactions were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials. The most common adverse reactions to pembrolizumab were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin reactions.
Efficacy and safety were based primarily on the modeling of dose/exposure relationships and observed pharmacokinetic data in patients with melanoma.
The recommended pembrolizumab doses for cSCC are 200 mg every three weeks or 400 mg every six weeks.
View full prescribing information for pembrolizumab.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.