Clin cancer research: EPZ-6438 combined with R-CHOP to treat diffuse large B-cell lymphoma.

BACKGROUND: Histoprotein methyl transferase EZH2 is a catalytic sub-base of the PRC2 complex involved in transcription regulation, and about 25% of patients with B-cell lymphoma carry the gene mutation.
oral EZH2 inhibitor tazemetostat (EPZ-6438) can target abnormal proliferation that relies on EZH2 activity.
method: This is a Phase I clinical trial that evaluates the safety of EPZ-6438 combined R-CHOP for newly diagnosed diffuse large B-cell lymphoma in 60-80 years of age, and identifies the recommended dose (RP2D) for the Phase II trial of EPZ-6438.
result: 17 patients were recruited.
2 cases of dose-limiting toxicity were observed during C1 and C2: 1 case of stage 3 constipation (400 mg) and 1 case of stage 5 lung infection (800 mg).
level 3 toxic effects in patients with more than 10% of patients were constipation (24%), nausea (12%) and hypokalemia (12%).
8 patients (47%) had hematological side effects of level 3-4: lesions (47%), leumaremia (29%), anemia (18%) and plateiac reduction (12%).
EPZ-6438 has an RP2D of 800 mg.
increase in the dose of EPZ-6438 did not increase toxicity to organs.
800 mg dose, the AAUC and Cmax of EPZ-6438 are similar to erdrug studies (E7438-G000-101).
: EpZ-6438 combined with R-CHOP RP2D is 800 mg 2/day.
security and PK are as relevant as single-use R-CHOP.
initial efficacy data are encouraging and deserve further validation in Phase II trials.
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