Pembrolizumab Receives FDA Accelerated Approval for Alternative Dosing Schedule
Posted: Friday, May 1, 2020
On April 28, the U.S Food and Drug Administration (FDA) granted accelerated approval to a new dosing regimen for the PD-1 inhibitor pembrolizumab (Keytruda) for all currently approved adult indications. The approved dosing schedule consists of administering 400 mg of pembrolizumab every 6 weeks, in addition to the current dosing schedule of 200 mg prescribed every 3 weeks. Pembrolizumab is currently used as a treatment for adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma.
The accelerated approval was based on pharmacokinetic modeling data, the drug’s relationship of exposure to efficacy, and its relationship of exposure to safety. The data compared the predicted exposure of pembrolizumab 400 mg every 6 weeks with observed exposures of pembrolizumab in patients who received pembrolizumab at 2 mg/kg every 3 weeks, 200 mg every 3 weeks, and 10 mg/kg every 2 weeks.
The pharmacokinetic modeling data were supported by data from a cohort of patients (Cohort B) in the KEYNOTE-555 trial. This international, single-arm, multicenter trial enrolled 101 patients with advanced or metastatic melanoma with no prior exposure to PD-1, PD-L1, or CTLA-4 inhibitors other than CTLA-4 inhibitors in the adjuvant setting. The study found the overall response rate in the first 44 patients was 39% (95% confidence interval = 24%–55%).
Severe or fatal immune-mediated adverse reactions associated with pembrolizumab include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation.
For more information on pembrolizumab, see the full prescribing information.
