FDA Approves Every-6-Week Pembrolizumab Dosage

A new dosage for pembrolizumab of 400 mg administered every 6 weeks across all adult indications has been approved by the FDA, whether the PD-1 inhibitor is used as monotherapy or in a combination regimen.

The FDA has approved a new dosage for pembrolizumab (Keytruda) of 400 mg administered every 6 weeks across all adult indications, whether the PD-1 inhibitor is used as monotherapy or in a combination regimen.1

The manufacturer, Merck, noted that this approval is especially important in light of reduced clinic visits to protect patients with cancer due to the coronavirus disease 2019 (COVID-19) pandemic.

“The important social distancing measures for COVID-19 have created a number of challenges for people with cancer, including keeping to planned treatment schedules,” said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in a statement. “Today’s approval of an every 6-week dosing schedule for Keytruda gives doctors an option to reduce how often patients are at the clinic for their treatment.”

The prior dosage for pembrolizumab, 200 mg every 3 weeks, will also still be a dosage option.

Pembrolizumab is associated with immune-mediated adverse reactions that can be severe or fatal in patients, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, and solid organ transplant rejection, as well as complications of allogeneic hematopoietic stem cell transplant. If these reactions occur, treatment should be withheld or discontinued based on the severity of the reaction, and corticosteroids can be used when appropriate.

This approval comes based on pharmacokinetic modeling and simulation data that were presented at the 2018 American Society of Oncology (ASCO) Annual Meeting. The 400 mg dose of pembrolizumab was submitted in a supplemental Biologics License Application to the FDA earlier in April 2020.

Findings from a cohort of the KEYNOTE-555 trial of patients with metastatic melanoma receiving the 400-mg every-6-weeks dosing schedule were presented recently at the 2020 American Association for Cancer Research Virtual Annual Meeting.2

One hundred patients with unresectable stage III or IV melanoma who had not received prior systemic therapy for unresectable/metastatic disease received the flexible treatment schedule and were compared with historical findings for similar patients who had received the 200-mg dose.

Pembrolizumab trough concentrations were similar between the 2 dosing schedules, and peak concentrations at the 400-mg dose were lower than that seen with the 10 mg/kg every 2 week dose of pembrolizumab, which is the highest clinical dose of pembrolizumab that has been shown to be safe.

As of the interim analysis for cohort B of the KEYNOTE-555, the objective response rate (ORR) was 38.6%. This was compared with combined experience from other clinical trials of pembrolizumab at the previously approved dosing schedules in patients with metastatic melanoma that showed an overall ORR of 35.1%.

Progression-free survival data were not yet mature in the cohort, but were expected to be similar to historical findings with prior doses.

The safety profile in the cohort was also consistent with the known safety profile from trials with the 200-mg every-3-weeks schedule that has been demonstrated in more than 12 different tumor types.

Observed pharmacokinetic exposures with pembrolizumab administered every 6 weeks in patients with melanoma were also expected to be similar across tumor types.

The investigators concluded that the ever-6-week dose was a more flexible and convenient option for both patients and physicians.

Pembrolizumab is currently under evaluation in over 1200 clinical trials in a wide variety of cancer types, as well as different treatment settings.1

Pembrolizumab has already been approved across many other disease types, which include non–small cell lung cancer, small cell lung cancer, head and neck squamous cell cancer, urothelial carcinoma, non-muscle invasive bladder cancer, microsatellite instability-high cancer, esophageal cancer, cervical cancer, and renal cell carcinoma.


  1. FDA Approves Merck’s KEYTRUDA (pembrolizumab) for Use at an Additional Recommended Dose of 400 mg Every Six Weeks for All Approved Adult Indications [news release]. Kenilworth, NJ: Merck; April 28, 2020. LINK. Accessed April 28, 2020.
  2. Lala M, Akala O, Chartash E, et al. Pemrbolizumab 400 mg Q6W Dosing: First Clinical Outcomes Data from KEYNOTE-555 Cohort B in Patients With Metastatic Melanoma. Presented at: 2020 AACR Virtual Annual Meeting; April 27-28, 2020. Abstract CT042.
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