Open-Label, Multicentre, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Adv. Solid Tumours or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With DLBCL

Official Title

An Open-Label, Multicentre, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Advanced Solid Tumours or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With Diffuse Large B Cell Lymphoma

Summary:

This is a multicentre, open-label, Phase 1/2 study that is being conducted in two parts. The Phase 1 part (closed to accrual as of January 25, 2016) is comprised of dose escalation and expansion parts to establish the MTD and/or the recommended Phase 2 dose (RP2D) when tazemetostat is given BID (twice daily) orally on a continuous basis. Additionally, in separate cohorts in Phase 1, the effect of food on the bioavailability of tazemetostat as well as the drug-drug interaction (DDI) potential of tazemetostat are being evaluated. The Phase 2 part was initiated once the MTD and /or RP2D was established. Phase 2 enrolls subjects with DLBCL (Cohorts 1-3 and 6) and FL (Cohorts 4 and 5) for the determination of efficacy and safety of tazemetostat monotherapy (Cohorts 1-5) and of tazemetostat in combination with prednisolone (Cohort 6) with placement determined by centrally confirmed histology, cell of origin (COO), and EZH2 mutation status.

Trial Description

Primary Outcome:

  • Maximum tolerated dose (MTD) (Phase 1 only)
  • Objective response rate (ORR; complete response + partial response [CR + PR]) (Phase 2)
Secondary Outcome:
  • The effect of a high fat meal on the bioavailability of tazemetostat (Phase 1)
  • The effect of tazemetostat on exposure of midazolam, a CYP3A4 substrate
  • To assess the preliminary activity of tazemetostat (Phase 1)
  • The effect of tazemetostat monotherapy and tazemetostat in combination with prednisolone on progression-free survival (PFS) (Phase 2)
  • The effect of tazemetostat monotherapy and tazemetostat in combination with prednisolone on duration of response (DOR) (Phase 2)
  • The safety and tolerability of tazemetostat monotherapy and tazemetostat in combination with prenisolone (Phase 1 and Phase 2)
  • The pharmacokinetic (PK) profile of tazemetostat monotherapy and tazemetostat in combination with prednisolone (Phase 1 and Phase 2)
  • The effect of tazemetostat monotherapy and tazemetostat in combination with prednisolone on overall survival (OS)

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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