FDA Approves New Dosing Regimen for Pembrolizumab

April 30, 2020

On April 28, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-new-dosing-regimen-pembrolizumab) to a new dosing regimen of 400 mg every six weeks for pembrolizumab (Keytruda®) across all currently approved adult indications, in addition to the current dosing regimen of 200 mg every three weeks. 

FDA Approves New Dosing Regimen for Pembrolizumab

“The new dosing regimen for pembrolizumab allows for less frequent trips to infusion center, which could reduce opportunities for patient exposure to COVID-19,” Lisa Kennedy Sheldon, PhD, ANP-BC, AOCNP®, FAAN, ONS’s clinical and scientific affairs liaison, said. 

Approval was based on pharmacokinetic modeling and exposure-response analyses that compared the predicted exposure of pembrolizumab at 400 mg every six weeks to observed exposures of pembrolizumab in patients who received pembrolizumab at 2 mg/kg every three weeks, 200 mg every three weeks, and 10 mg/kg every two weeks.  

A cohort of 101 patients with advanced or metastatic melanoma who had not received prior PD-1, PD-L1, or CTLA-4 inhibitors (other than CTLA-4 inhibitors in the adjuvant setting) were enrolled an international, single-arm, multicenter study (KEYNOTE-555; NCT03665597). The pharmacokinetic modeling was supported by additional exposure-response analyses across the pembrolizumab development program and an interim analysis of pharmacokinetics and overall response rate (ORR). ORR was 39% (95% CI = 24, 55) in the first 44 patients enrolled in KEYNOTE-555. 

For additional safety and efficacy information and recommended dosing regimens, view the full prescribing information for pembrolizumab (https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125514s059s064s076s083lbl.pdf)

The new dosing regimen received accelerated approval based on pharmacokinetic data, the relationship of exposure to efficacy, and the relationship of exposure to safety. Continued approval for the indication may be contingent on verification and description of clinical benefit in confirmatory trials. 

The application was approved more than five months prior to the FDA goal date. 

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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) 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 (mailto:OncProjectFacilitate@fda.hhs.gov).  

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