Keytruda (pembrolizumab) significantly extends survival without disease worsening in adults with relapsed or refractory classical Hodgkin’s Lymphoma (cHL), compared to treatment with Adcetris (brentuximab vedotin), interim data from a Phase 3 pivotal trial show.
“Patients with classical Hodgkin lymphoma are generally young and when they do not achieve remission following standard treatment, their cancer is challenging to treat,” Jonathan Cheng, MD, vice president of oncology clinical research, at Merck Research Laboratories, said in a press release.
Keytruda, by Merck, is a PD-1 inhibitor indicated for several types of blood and solid tumors. The medicine was granted accelerated approval in March 2017 by the U.S. Food and Drug Administration (FDA) for the treatment of adults and children with refractory cHL who have relapsed after three or more prior lines of therapy. In the same year, Keytruda was also approved by the European Commission as a treatment for cHL.
The FDA’s decision was based on data from 210 patients enrolled in the KEYNOTE-087 Phase 2 trial (NCT02453594), showing that after a median 9.4 months of follow-up, 69% of the patients were responding well to the therapy, with 22% achieving complete remission and 47% achieving partial remission. The median duration of response was 11.1 months.
Given the FDA’s accelerated approval of Keytruda for cHL, the treatment’s continued authorization may be contingent upon verification and description of clinical benefit in confirmatory trials.
The KEYNOTE-204 Phase 3 trial (NCT02684292) is a confirmatory trial for the medicine’s current indication in cHL, aiming to evaluate the use of single therapy with Keytruda versus Adcetris for the treatment of patients with relapsed or refractory cHL.
The study has two primary goals (primary endpoints) — the length of time the patient lives without the disease worsening, or progression-free survival, and patients’ overall survival.
Secondary endpoints include the proportion of patients with a reduction in tumor burden (objective response rate), those who reached complete remission, as well as safety.
The trial enrolled 304 patients, age 18 years or older, who were randomized to receive either Keytruda or Adcetris by intravenous infusions, on the first day of each three-week cycle, for up to 35 cycles.
A preliminary analysis conducted by an independent committee shows that patients treated with Keytruda lived significantly longer without worsening disease, compared to those given Adcetris — an improvement Merck says was “statistically significant and clinically meaningful.”
Keytruda’s safety profile was consistent with prior studies, and no new safety signals were observed for patients given the therapy. The assessment of the other primary endpoint of the trial — overall survival — is still ongoing.
These results will be shared at an upcoming meeting and submitted to regulatory authorities, Merck says.
“These pivotal [P]hase 3 data indicate a statistically significant and clinically meaningful improvement in progression-free survival with Keytruda compared, in head to head fashion, with the currently approved therapy of brentuximab vedotin [Adcetris],” Cheng said. “These data are strongly supportive of Keytruda’s current indication in cHL and we plan to file these data with regulatory authorities as quickly as is possible.”
Keytruda is an anti-PD-1 therapy that works by enhancing the ability of the body’s immune system to help detect and kill tumor cells. It is an antibody that specifically binds to and blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Certain tumors use the PD-1 pathway to resist the body’s immune system. By blocking it, Keytruda is thought to activate immune T-cells with the ability to detect and fight cancer cells.
