Chronic Myeloid Leukemia, Chronic Myeloid Leukemia, Chronic Phase
Conditions
Keywords
allosteric inhibitor of BCR-ABL1, CML, TERN-701, chronic myeloid leukemia, T315I, T315I mutant, CARDINAL, HS-10382
Brief 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).
Interventions
DRUGTERN-701
TERN-701 orally QD
Sponsors
Terns, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A sequential Intervention Model was used for Part 1 Dose Escalation. In the Part 2 Randomized Dose Expansion, participants will be randomized to one of two selected doses in parallel for the duration of the study. Participants enrolled into Part 2m (mutational cohort) will receive the same selected dose
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Australia, France, Germany, Italy, New Zealand, South Korea, Spain, United Kingdom, United States
Contacts
Primary ContactStudy Director
Outcome results
None listed