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).
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
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)
Parallel
TERN-701
DrugTERN-701 orally QD
7
Treatment groupsSee each treatment group below.
Part 1 - Incidence of Dose Limiting Toxicities during the first cycle of treatment
Determination of the Maximum Tolerated Dose (MTD) and recommended doses for expansion cohorts of TERN-701.
Part 1 - Serious Adverse Events
Number and percentage of patients with any serious adverse event
Part 1 - Adverse Events
Number and percentage of patients with any adverse event
Part 2- Complete Hematologic Response (CHR)
CHR Defined by ELN 2020 criteria in participants who are not in CHR at baseline.
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