A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas

Description

The study is divided into Phase 1 and Phase 2. In Phase 1 and the Phase 2 expansion (M1 to M7), patients are non-randomized. In Phase 2 optimization, patients in Cohort M2 and M3 (Stage 2a and 2b) and Cohort M8 (Part 2) are randomized.

Phase 1 of the study is composed of a Tulmimetostat Dose Escalation period in patients with advanced tumors and aims to determine maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of Tulmimetostat as monotherapy in patients with advanced tumors.

Phase 2 of the study is planned to evaluate safety and tolerability and antitumor activity of Tulmimetostat in six disease-specific cohorts (M1 to M6). Patients in Cohorts M1, M2, M3, M5, and M6 will be enrolled at 10 to 29 patients per cohort, using a Simon 2-stage design. Cohort M4 will enroll up to 20 patients with lymphoma in a single-stage.

The primary aim of Phase 2 part of the study is to evaluate the antitumor activity of Tulmimetostat, and characterize the safety and tolerability of Tulmimetostat as monotherapy in patients with selected tumors.

In Phase 2, two additional doses are planned to be evaluated in cohorts M2 and M3 in 2 stages: Stage 2a and Stage 2b. In Stage 2a approximately 20 patients will be enrolled per cohort and will be randomized 1:1 to receive 2 prespecified dose levels of Tulmimetostat once daily. When protocol criteria for initiating Stage 2b will be fulfilled after completion of Stage 2a, then Stage 2b will be opened for enrolment of additional 10 patients in one or both dose arms in each of the two cohorts. Thus, up to 40 patients per cohort (M2 and M3) could be enrolled.

The study will explore the Tulmimetostat in anti-tumor activity and effect of food on pharmacokinetics of Tulmimetostat in in patients with ARID1A WT endometrial carcinoma (Cohort M7) and safety and anti-tumor activity of Tulmimetostat in in combination with enzalutamide in patients with mCRPC (Cohort M8).

In Cohort M8 Part 1, the safety and tolerability of Tulmimetostat in and enzalutamide combination will be evaluated in patients with mCRPC. The M8 Part 1 dose escalation incorporates combination of Tulmimetostat in at escalating provisional doses with enzalutamide.

In Cohort M8 Part 2, the safety, tolerability and preliminary antitumor activity of Tulmimetostat at a RP2D in combination with enzalutamide will be further evaluated in patients with mCRPC.