A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL)

Overview

The goal of the study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of TERN-701, a highly selective allosteric inhibitor of BCR-ABL1, in participants with previously treated chronic phase - chronic myeloid leukemia (CP-CML). The study has two parts: Part 1 of the trial (Dose Escalation) will evaluate sequential dose escalation cohorts of TERN-701 administered once daily. Part 2 (Dose Expansion) consists of randomized, parallel dose expansion cohorts of TERN-701 that will further evaluate the efficacy and safety of 2 recommended dose levels for expansion selected from Part 1. Part 2m (mutation cohort) will further evaluate the efficacy and safety of 500mg of TERN-701 in previously treated CP-CML participants with certain resistance mutations. In both Part 1 and Part 2, participants will receive continuous once daily dosing of TERN-701 divided into 28-day cycles. During the treatment period, participants will have scheduled visits to the trial center at Cycle 1 day 1(C1D1), C1D2 (Part 1 only), C1D8, C1D15, and C1D16 (Part 1 only), followed by Day 1 of Cycles 2 through 7, and Day 1 of every 3 cycles thereafter. Approximately 180 participants could be enrolled in this trial, up to 80 participants in Part 1 (dose escalation), including optional backfill cohorts, approximately 80 participants in Part 2 (randomized dose expansion), and approximately 20 participants in Part 2m (mutation cohort). All participants will receive active trial intervention. Four dose-level cohorts have been evaluated in Part 1; two dose levels will be evaluated in Part 2 (Randomized Dose Expansion), and one dose level will be evaluated in Part 2m (mutation cohort).