A Study on the Effect of E7438 in Patients with Advanced Tumors
Research type
Research Study
Full title
An Open-Label, Multicenter, Phase 1/2 Study of E7438 (EZH2 Histone Methyl Transferase [HMT] inhibitor) as a Single Agent in Subjects With Advanced Solid Tumors or With B cell Lymphomas
IRAS ID
154916
Contact name
Peter Johnson
Contact email
Sponsor organisation
Epizyme, Inc.
Eudract number
2012-004083-21
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
14/SC/1195, Previous REC application REC reference number
Duration of Study in the UK
4 years, 0 months, 18 days
Research summary
This is a study of an investigational drug, called E7438 (enhancer of zeste homolog 2 [EZH2] Histone Methyl Transferase [HMT] Inhibitor) to treat patients with Advanced solid tumors or with B cell Lymphomas.
It is a multicenter, open-label, Phase 1/2 study that will be conducted in 2 parts. The Phase 1 part will comprise dose escalation and establishment of the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) when E7438 is given BID orally on a continuous basis in subjects with histologically and/or cytologically confirmed advanced or metastatic solid tumors or B cell lymphomas that have progressed after treatment with approved therapies or for which there are no standard therapies available.
Additionally, in separate cohorts in Phase 1, the effect of food on the bioavailability of E7438 will be evaluated as well as the drug-drug interaction (DDI) potential as evaluated by the effect of E7438 on the pharmacokinetics of midazolam, a CYP3A4 substrate.
Phase 2 will enroll subjects with B cell lymphoma for the determination of efficacy and safety of E7438 in 4 independently analyzed cohorts determined by histology and (EZH2) mutation status. Eligible subjects will be EZH2 gene mutation positive or negative (wild-type) with histologically confirmed diffuse large B cell lymphoma (DLBCL of either germinal center origin [GCB] or primary mediastinal subtypes) or follicular lymphomas (FL) (Grades 1 to 3), with relapsed or refractory disease.
Approximately 189 subjects are expected to take part in the study, from up to 40 hospitals worldwide.
After undergoing certain screening procedures, eligible subjects will be enrolled in the trial. Whilst on study, subjects will undergo safety and tumour assessments, as well as pharmacokinetic, pharmacodynamic, biomarker and pharmacodynamic assessments. Subjects may remain on study until they have disease progression, development of unacceptable toxicity that leads to E7438 treatment withdrawal, or withdrawal of consent.
REC name
South Central - Berkshire Research Ethics Committee
REC reference
15/SC/0003
Date of REC Opinion
2 Feb 2015
REC opinion
Favourable Opinion