In a phase I study reported in The Lancet Oncology, Maruyama et al found that valemetostat—a novel dual inhibitor of EZH2 and EZH1—showed activity in patients with relapsed or refractory non-Hodgkin lymphoma.
Study Details
In the study, 90 patients from sites in Japan and the United States were enrolled between April 2016 and June 2021 in dose-escalation and dose-expansion phases. A total of 54% of patients were Asian.
In the dose-escalation phase, patients received oral valemetostat at doses of 150 mg, 200 mg, 250 mg, or 300 mg per day continuously in 28-day cycles until disease progression or unacceptable toxicity. All patients in the dose-expansion phase received 200 mg per day.
Key Findings
Overall, 7 patients (8%) received valemetostat at 150 mg per day, 74 (82%) received 200 mg per day, 7 (8%) received 250 mg per day, and 2 (2%) received 300 mg per day. Median follow-up was 7.4 months (interquartile range = 3.4–17.6 months). Maximum tolerated dose was not reached, with the recommended phase II dose being 200 mg per day.
The most common adverse events of any grade were decreased platelets (58%), dysgeusia (50%), and anemia (42%). The most common grade 3 or 4 adverse events were decreased neutrophils (23%), decreased platelets (20%), and decreased lymphocytes (19%). The most common serious adverse event of any grade was Pneumocystis jirovecii pneumonia (4%). No treatment-related deaths were observed.
Among 88 patients evaluable for response, objective response was observed in 48 patients (54.5%, 95% confidence interval [CI] = 43.6%–65.2%), with a complete response in 23 (26%). Objective responses were observed in 30 of 55 patients (54.5%, 95% CI = 40.6%–68.0%) with peripheral T-cell lymphoma, 9 of 14 (64.3%,95% CI = 35.1%–87.2%) with adult T-cell leukemia/lymphoma, and 9 of 19 (47.4%, 95% CI = 24.4%–71.1%) with B-cell non-Hodgkin lymphoma. Median response durations were 21.9 months, 21.2 months, and 18.4 months in responders in the three subgroups, respectively.
The investigators concluded: “The safety profile of valemetostat monotherapy was acceptable in these patients with relapsed or refractory non-Hodgkin lymphoma. [Favorable] clinical activity was observed. These findings support a new indication for valemetostat in this setting.”
Dai Maruyama, MD, of the Department of Hematology, National Cancer Center Hospital, Tokyo, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Daiichi Sankyo. For full disclosures of all study authors, visit The Lancet Oncology.
