FDA Approves New 400 mg Every-6-Weeks Dosing Regimen of Keytruda for All Indications

Web Exclusives - FDA Updates

On April 28, 2020, the FDA accelerated the approval of a new dosing regimen—400 mg every 6 weeks—for the PD-1 inhibitor pembrolizumab (Keytruda; Merck) for all its many indications currently approved by the FDA for adults. This new dosing regimen is now available as an option in addition to the previously approved dosing regimen of 200 mg every 3 weeks for this immunotherapy. The availability of an every-6-weeks dosing regimen instead of the every-3-weeks administration of an intravenous medication, which requires a visit to a provider’s office or clinic, is great news for patients, as well as for oncology providers.

“The importance of social distancing measures for COVID-19 have created a number of challenges for people with cancer, including keeping to planned treatment schedules,” said Roy D. Baynes, MD, PhD, SVP, Head of Global Clinical Development, and Chief Medical Officer, Merck Research Laboratory. “Today’s approval of an every-six-week dosing schedule for Keytruda gives doctors an option to reduce how often patients are at the clinic for their treatment.”

Pembrolizumab is currently indicated for 15 types of cancer (as monotherapy or in combination with other therapies), including melanoma; non–small-cell lung cancer; small-cell lung cancer; head and neck squamous-cell cancer; classical Hodgkin lymphoma; primary mediastinal large B-cell lymphoma; urothelial carcinoma; microsatellite instability-high (MSI-H) cancer in solid tumors; gastric cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel-cell carcinoma; renal-cell carcinoma; and endometrial carcinoma that is not MSI-H or dMMR (mismatch repair deficient).

The approval of the new dosing regimen was based on pharmacokinetic modeling and exposure-response analyses that were used to compare the predicted exposure of pembrolizumab 400 mg every 6 weeks with the observed exposures of this agent in patients who received pembrolizumab using 1 of 3 dosing regimens, including 2 mg/kg administered every 3 weeks; 200 mg given every 3 weeks; and 10 mg/kg administered every 2 weeks.

These pharmacokinetic modeling and exposure-response analyses were supported by additional exposure-response analyses across the full range of the drug development program for pembrolizumab, as well as an interim analysis of the overall response rate in 101 patients who were enrolled in the KEYNOTE-555 clinical trial. KEYNOTE-555 was an international, single-arm, multicenter study of patients with advanced or metastatic melanoma who had not received any PD-1, PD-L1, or CTLA-4 inhibitors (except for CTLA-4 inhibitors in the adjuvant setting). The overall response rate was 39% (95% confidence interval, 24-55) in the first 44 patients in that cohort.

This new dosing regimen was approved by the FDA under its accelerated approval protocol. Continued approval for this indication may be contingent on benefit verification from a confirmatory trial. This application was approved >5 months before the scheduled FDA target date.

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Last modified: July 22, 2021