The U.S. Food and Drug Administration (FDA) has expanded the use of Keytruda (pembrolizumab) as a second-line treatment for adults with relapsed or refractory classical Hodgkin’s lymphoma (cHL) for whom initial therapies did not work or stopped working.
The regulatory agency also updated an indication for children and adolescents with cHL, who may now be prescribed Keytruda after failing to respond (refractory) to at least one prior treatment, or when their cancer returns after a successful initial response (relapsed) to two or more lines of therapy.
Previously, the Merck therapy had gained conditional approval for the treatment of adults and children who had relapsed after three or more lines of therapy.
These approvals, granted after a priority review, were based on data from the KEYNOTE-204 Phase 3 clinical trial (NCT02684292), in which Keytruda significantly extended life without disease worsening compared with standard Adcetris (brentuximab vedotin) treatment.
“The patients with cHL who do not achieve remission following initial treatment or who relapse after transplantation face a poor prognosis, reflecting the unmet need for improved therapies in the relapsed/refractory setting,” John Kuruvilla, MD, a hematologist and associate professor of medicine, Princess Margaret Cancer Centre and University of Toronto, said in a press release.
“Now patients with cHL who progress after frontline therapy have a new option in Keytruda, which has demonstrated a clinically meaningful improvement in progression-free survival compared to brentuximab vedotin,” said Vicki Goodman, vice president of clinical research at Merck Research Laboratories.
Keytruda, developed by Merck (known as MSD outside the U.S. and Canada), is an immune checkpoint inhibitor that blocks a mechanism used by cancer cells to avoid being targeted and killed by immune cells.
It specifically prevents the PD-1 receptor found on the surface of immune T-cells from interacting with the PD-L1 protein produced by cancer cells, enabling immune cells to eliminate cancer with greater efficacy.
The treatment was conditionally approved for adults and children with cHL, based on promising findings from the KEYNOTE-087 Phase 2 trial (NCT02453594). There, 69% of patients responded to treatment, including 22% who saw complete cancer eradication, and their responses lasted a median of 11.1 months.
However, as happens with most accelerated approvals, a full approval of this medication for cHL patients was pending the confirmation of clinical benefits in a larger, randomized Phase 3 trial. That’s where KEYNOTE-204 comes in.
KEYNOTE-204 was designed to investigate whether Keytruda was better than standard-of-care therapies at delaying disease progression or death, and extending overall survival. A secondary goal was to measure the proportion of patients responding to both treatment approaches.
A total of 304 adults with relapsed or refractory cHL were randomly assigned to receive intravenous (into-the-vein) infusions of either Keytruda or standard Adcetris, given every three weeks for approximately two years.
Results showed that Keytruda significantly reduced the risk of disease progression or death by 35% — helping patients live without signs of disease worsening for a median of 13.2 months, compared with a median of 8.3 months in the Adcetris group.
The percentage of patients responding to treatment also was higher for Keytruda than for Adcetris (66% vs. 54%), although these differences were deemed not statistically significant. Still, responses lasted longer with Keytruda — a median of 20.7 months — compared with 13.8 months for Adcetris.
During the trial, patients received Keytruda for a median of 10 months. The most common adverse reactions in Keytruda-treated patients included respiratory infections (41%), musculoskeletal pain (32%), and diarrhea (22%). Fever, fatigue, rash, and cough also were common, each occurring in about 20% of patients.
Serious adverse reactions were observed in 30% of patients, and 14% discontinued treatment permanently due to an adverse reaction. Three patients died during the study due to causes not linked with disease progression
“With this approval, Keytruda has the potential to change the current standard of care and help these patients achieve better outcomes,” said Kuruvilla.
“At Merck, we are committed to improving outcomes for patients with cancer,” Goodman added. “Today’s FDA approval builds upon our growing range of options for people with blood cancers.”
Keytruda’s approval was reviewed under Project Orbis, an FDA initiative created to allow simultaneous submission and review of cancer medications among international regulatory partners. For this application, the FDA worked together with the Australian Therapeutic Goods Administration and Health Canada to review the medication.
