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).

Eligibility

Key Inclusion Criteria:

• Male or female participants ≥ 18 years of age at the time of signing the informed consent
• Have an ECOG performance status score of 0 to 2
• Have an established cytopathologically confirmed diagnosis of BCR-ABL1 positive CML in Chronic Phase
• Have received treatment with at least one prior TKI and have treatment failure, suboptimal response, or treatment intolerance
• Prior treatment with asciminib is allowed
• Adequate organ function, as assessed by local laboratory

Key Exclusion Criteria:

• Systemic antineoplastic therapy (including prior TKIs, interferon-alfa, therapeutic antibodies, chemotherapy) or other experimental therapy 7 days before the first dose of TERN-701
• Have completed previous anticancer therapy without resolution of all associated clinically significant toxicity (to ≤ Grade 2 or baseline)