Keytruda (pembrolizumab) has been recommended for approval in the European Union (EU) to treat adults and children, 3 years and older, with relapsed or refractory classical Hodgkin’s lymphoma (cHL) whose disease failed to respond to autologous stem cell transplant (ASCT) or who received at least two prior therapies when ineligible for ASCT.
The therapy is already available in Europe to adults with relapsed or refractory cHL whose disease progressed following ASCT and Adcetris (brentuximab vedotin), or who are transplant-ineligible and have failed to respond to Adcetris.
The recommendation was made by the Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency. The committee’s recommendations are generally accepted by the European Commission, which makes the final decisions.
A decision on Keytruda’s label expansion is expected in the upcoming months; if approved, it would mark the first pediatric indication for the therapy in the EU.
“This positive opinion reinforces the importance of Keytruda for certain adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma in the European Union,” Vicki Goodman, MD, vice president of clinical research at Merck Research Laboratories, said in a press release. Merck, known as MSD outside the U.S. and Canada, is the developer of Keytruda.
“We look forward to the decision by the European Commission and will continue to expand our clinical development program in blood cancers with Keytruda and our recently acquired investigational therapies to help address the unmet needs of patients,” Goodman added.
This potential label expansion would follow a similar decision in the U.S., which approved the expansion of Keytruda’s previous indication as a late-line treatment for children and adults with cHL to allow its use as a second- or third-line therapy.
An immune checkpoint inhibitor, Keytruda works by preventing an immune evasion mechanism involving the interaction between the PD-1 receptor in T-cells, which are immune cells involved in the fight against cancer, and the PD-L1 protein in cancer cells. As such, Keytruda is expected to boost anti-cancer immune responses and cancer cell death.
The CHMP’s positive opinion was based on data from the KEYNOTE-204 Phase 3 clinical trial (NCT02684292) and from an updated analysis of the KEYNOTE-087 Phase 2 trial (NCT02453594) — which supported EU-approval of Keytruda for the current cHL indication.
KEYNOTE-204 is evaluating whether Keytruda is superior to standard treatment Adcetris at extending survival and the time patients live without showing signs of disease progression in 304 adults with relapsed or refractory cHL.
Participants were randomly assigned to receive intravenous (into-the-vein) infusions of either Keytruda or Adcetris, every three weeks for about two years.
KEYNOTE-204’s latest data showed Keytruda-treated patients lived 4.9 months longer without signs of disease worsening than those on Adcetris (13.2 months vs. 8.3 months), representing a 35% lower risk of disease progression or death.
A greater proportion of patients receiving Keytruda also responded to treatment, compared with those treated with Adcetris (66% vs. 54%), although these differences did not reach statistical significance. Still, responses lasted longer in the Keytruda group than in the Adcetris group (median of 20.7 months vs. 13.8 months).
Keytruda’s safety profile was consistent with that reported in previous trials, with the most common adverse reactions being respiratory infections (41%), musculoskeletal pain (32%), and diarrhea (22%).
Treatment discontinuation due to adverse events occurred in 14% of patients in the Keytruda group. Three Keytruda-treated patients (2%) died from causes other than disease progression: two from complications after ASCT and one from an unknown cause.
Keytruda is also approved in the U.S. and EU for the treatment of different types of cancer, including lung, bladder, stomach, esophageal, and liver cancer, melanoma (a type of skin cancer), and cancers with specific genetic features that failed prior therapies. The therapy is being evaluated in several trials of cHL and other blood cancers.