A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL)
Purpose
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).
Conditions
- Chronic Myeloid Leukemia, Chronic Phase
- Chronic Myeloid Leukemia
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
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)
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- 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
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1- Dose Level 1 (160 mg) of TERN-701 |
Dose Level 1 of TERN-701 dosed once daily. |
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|
Experimental Part 1- Dose Level 2 (320 mg) of TERN-701 |
Dose Level 2 of TERN-701 dosed once daily. |
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|
Experimental Part 1- Dose Level 3 (400 mg) of TERN-701 |
Dose Level 3 of TERN-701 dosed once daily. |
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|
Experimental Part 1- Dose Level 4 (500 mg) of TERN-701 |
Dose Level 4 of TERN-701 dosed once daily. |
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|
Experimental Part 2 - Dose 1 (320 mg) |
Dose 1 was selected based on the totality of safety, PK, PD and efficacy data from Part 1. TERN-701 administered once daily. |
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Experimental Part 2 - Dose 2 (500 mg) |
Dose 2 was selected based on the totality of safety, PK, PD and efficacy data from Part 1. TERN-701 administered once daily. |
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|
Experimental Part 2m - 500 mg Dose |
Dose for Part 2m was selected based on the totality of safety, PK, PD and efficacy data from Part 1 and nonclinical data. TERN-701 is administered once daily. |
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Recruiting Locations
Birmingham 4049979, Alabama 4829764 35233
More Details
- Status
- Recruiting
- Sponsor
- Terns, Inc.