Clin Cancer Research: Tazemetostat (EPZ-6438) Joint R-CHOP treatment of diffuse large B cell lymphoma

BACKGROUND: Histone methyl metastase EZH2 is the catalytic sub-base of the PRC2 complex involved in transcription regulation, with about 25% of patients with birth center B cellslymphomacarrying the gene mutationOral EZH2 inhibitor tazemetostat (EPZ-6438) can target abnormal proliferation that relies on EZH2 activitymethod: This is a Phase Ib clinical trial that evaluates the safety of EPZ-6438 joint R-CHOP for newly diagnosed diffuse large B-cell lymphoma sepsis aged 60-80 years, and identifies the recommended dose (RP2D) for EPZ-6438 Phase IIresult: a total of 17 patients were recruitedDuring C1 and C2, a total of 2 dose-restrictive toxicity cases were observed: 1 case of level 3 constipation (400 mg) and 1 case of level 5 lunginfection(800 mg)The toxic effects of the level 3 in the s3 patients were constipation (24%), nausea (12%) and hypokalemia (12%)Eight (47%) patients experienced level 3-4 hematologic side effects: neutrophil reduction (47%), leukocyte reduction (29%), anemia (18%) and platelet reduction (12%)The RP2D for epZ-6438 is 800 mgThe increase in the dose of EPZ-6438 did not increase the toxicity of organsAt 800 mg doses, the AUC and Cmax of EPZ-6438 are similar to those in the single drug study (E7438-G000-101)Conclusion: The RP2D, which is jointwithd by EPZ-6438 and R-CHOP, is 800 mg 2/dayThe correlation between security and PK is comparable to that of single-use R-CHOP The initial efficacy data are encouraging and warrant further validation of Phase II trials