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

Condition(s) studied

Investigational drug(s) / intervention(s)

TERN-701: TERN-701 orally QD

Study summary

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

Primary outcome measure(s)

• Part 1 - Incidence of Dose Limiting Toxicities during the first cycle of treatment — First cycle is 28 days
  Determination of the Maximum Tolerated Dose (MTD) and recommended doses for expansion cohorts of TERN-701.
• Part 1 - Serious Adverse Events — up to 3 years
  Number and percentage of patients with any serious adverse event
• Part 1 - Adverse Events — up to 3 years
  Number and percentage of patients with any adverse event
• Part 2- Complete Hematologic Response (CHR) — up to 3 years
  CHR Defined by ELN 2020 criteria in participants who are not in CHR at baseline.
• Part 2: Molecular response (MR) — up to 3 years
  MR defined by ELN 2020 criteria measured by quantitative polymerase chain reaction of BCR-ABL transcript levels.
• Part 2 - Best categorical shift in BCR-ABL1 transcript levels from baseline — up to 3 years
  The best categorical molecular response shift on treatment relative to baseline

Trial sites (54)

+ 14 more sites — see the full list on the official registry below.

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