The FDA has accepted 6 supplemental Biologics License Applications (sBLAs) for review for a potential update to the dosing schedule for pembrolizumab across several indications.
The FDA has accepted 6 supplemental Biologics License Applications (sBLAs) for review for a potential update to the dosing schedule for pembrolizumab (Keytruda) across several indications.1
The sBLAs are seeking to include an every-6-weeks dosing schedule option for 400 mg of pembrolizumab infused over 30 minutes for patients with melanoma, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, gastric cancer, hepatocellular carcinoma, and Merkel cell carcinoma. The agency has set a target action date of February 18, 2020.
“We are committed to improving cancer care, which includes identifying ways to ensure patients have a flexible dosing option that may reduce the amount of time they spend receiving treatment,” Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories, said in a statement. “If approved, the 6-week dosing schedule will provide physicians and patients with greater flexibility in their treatment plans across a variety of cancer types, including melanoma where Keytruda is indicated in both the adjuvant and metastatic settings. We look forward to working with the FDA to file additional Keytruda dosing sBLAs later this year.”
The European Commission approved this dosing schedule in the European Union on March 28, 2019, for all of the PD-1 inhibitor’s monotherapy indications, including nonsmall cell lung cancer, head and neck squamous cell carcinoma, urothelial carcinoma, microsatellite instability–high or mismatch repair deficient solid tumors, and cervical cancer.
Pembrolizumab is currently approved in the United States for many indications at a dose of either 200 mg or 2 mg/kg every 3 weeks infused over 30 minutes. If the newer schedule was approved as an additional dosing option for patients, it would apply for the following indications:
A pharmacokinetics analysis of the 400 mg every-6-weeks dosing schedule tested safety and exposures compared with the approved doses.2The 400 mg every-6-weeks dosing regimen had similar predicted exposures to the 200 mg every-3-weeks regimen and clinical outcomes were expected to be similar with the newer schedule.
The geometric mean of the predicted peak concentrations at steady state for the 400 mg every-6-weeks regimen was about 65% lower than that of the 10 mg/kg every-2-weeks schedule.
Investigators expected the every-6-weeks schedule would produce similar efficacy, safety, and benefit-risk profile to the approved regimen with a more convenient schedule for patients.