The U.S. Food and Drug Administration (FDA) has accepted and given priority review to Merck‘s application requesting the approval of Keytruda (pembrolizumab) as a second-line treatment for adults with relapsed or refractory classical Hodgkin’s lymphoma (cHL).
The supplemental biologics license application was based on data from the Phase 3 KEYNOTE-204 clinical trial (NCT02684292), in which Keytruda significantly extended life without disease worsening compared with standard Adcetris (brentuximab vedotin).
The agency has set a Prescription Drug User Fee Act (PDUFA) action date for Oct. 30, meaning it will make a decision on whether to approve Keytruda for this indication by then.
“Classical Hodgkin lymphoma accounts for more than nine in 10 cases of Hodgkin’s lymphoma, which impacts approximately 7,400 patients a year in the U.S. For patients with classical Hodgkin lymphoma who do not achieve remission after first-line treatment, there is a particularly poor prognosis due to the limited options available,” Jonathan Cheng, vice president of oncology clinical research at Merck, said in a press release.
“We look forward to working with the FDA to bring Keytruda to more patients with classical Hodgkin’s lymphoma after initial treatment,” Cheng added.
Keytruda is an immune checkpoint inhibitor that prevents the PD-1 receptor found on the surface of immune T-cells from interacting with the PD-L1 protein produced by cancer cells. In this way, the medication disrupts one of the mechanisms cancer cells use to avoid being targeted and destroyed by the body’s immune system.
Keytruda, developed by Merck (known as MSD outside the U.S. and Canada), has been approved in the U.S. and the EU to treat a variety of cancer types, including lung, bladder, stomach, esophageal, and liver cancers.
It also received accelerated approval from the FDA in 2017 for the treatment of adults and children with refractory cHL, or who relapsed after receiving three or more prior lines of therapy. In addition to supporting the current request for approval, the pivotal KEYNOTE-204 study is the confirmatory trial for this accelerated approval indication.
KEYNOTE-204 was designed to assess if Keytruda was better than Adcetris (brentuximab vedotin) at extending survival and prolonging the time patients with relapsed or refractory cHL lived without showing signs of disease worsening.
It enrolled 304 adults, who were randomly assigned to receive intravenous (into-the-vein) infusions of either Keytruda or Adcetris, once per three-week cycle, for up to 35 cycles.
A preliminary analysis conducted by an independent committee found patients receiving Keytruda in KEYNOTE-204 lived longer without showing signs of disease progression than those on Adcetris.
The latest data, recently presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program, confirmed these findings, with Keytruda prolonging the time patients lived without disease worsening from a median of 8.3 to 13.2 months — representing a 35% lower risk of disease progression or death.
The proportion of patients showing no signs of disease progression after one year was also higher among those receiving Keytruda than in those given Adcetris (53.9% vs. 35.6%).
Importantly, these benefits were seen across all patient subgroups, including those with primary refractory disease (patients whose disease returned less than a year after completing their first-line therapy) and those who never received a stem cell transplant.
The percentage of patients responding to treatment was also higher among those on Keytruda (65.6%) than in those on Adcetris (54.2%). Treatment responses also lasted longer with Keytruda (20.7 months), compared with 13.8 months for Adcetris.
The incidence of severe, life-threatening, and fatal adverse events was slightly higher in the group of patients receiving Adcetris (25% vs. 19.6%). One patient on Keytruda died of pneumonia during the study.
Based on these findings, the investigators concluded that Keytruda was superior to Adcetris at prolonging the time patients lived without disease progression, and “should be standard of care for [patients with relapsed or refractory cHL].”