CARDINAL- A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia

Study Overview
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Brief Summary
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The goal of the study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of TERN-701, a novel 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 at least 2 recommended dose levels for expansion selected from Part 1. In both Part 1 and Part 2, participants will receive continuous 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, C1D8, C1D15, and C1D16, followed by Day 1 of Cycles 2 through 7, and Day 1 of every 3 cycles thereafter. Approximately 60 to 80 participants could be enrolled in this trial, including approximately 24 to 36 participants in Part 1 (dose escalation), including optional backfill cohorts, and approximately 40 participants in Part 2 (randomized dose expansion). All participants will receive active trial intervention. Up to 4 dose-level cohorts may be evaluated in Part 1; at least 2 dose levels may be evaluated in Part 2.

Official Title
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A Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia

Conditions
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Chronic Myeloid Leukemia, Chronic Phase, Chronic Myeloid Leukemia

Intervention / Treatment
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* Drug: TERN-701


Participation Criteria
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Eligibility Criteria
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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 with or without T315l mutation Have received treatment with active site targeting TKIs and have treatment failure, suboptimal response, or treatment intolerance Participants who are intolerant of asciminib, and do not have resistant/relapsing disease Adequate organ function, as assessed by local laboratory Key Exclusion Criteria: CML in accelerated or blast phase 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1- Dose Level 1 of TERN-701<br>Dose Level 1 of TERN-701 dosed once daily. | Drug: TERN-701<br>* TERN-701 orally QD<br>|
| Experimental: Part 1- Dose Level 2 of TERN-701<br>Dose Level 2 of TERN-701 dosed once daily. | Drug: TERN-701<br>* TERN-701 orally QD<br>|
| Experimental: Part 1- Dose Level 3 of TERN-701<br>Dose Level 3 of TERN-701 dosed once daily. | Drug: TERN-701<br>* TERN-701 orally QD<br>|
| Experimental: Part 1- Dose Level 4 of TERN-701<br>Dose Level 4 of TERN-701 dosed once daily. | Drug: TERN-701<br>* TERN-701 orally QD<br>|
| Experimental: Part 2 - Dose 1<br>Dose 1 will be selected from Part 1 based on the totality of safety, PK, PD and efficacy data from Part 1 will be selected. TERN-701 is planned to be administered once daily. | Drug: TERN-701<br>* TERN-701 orally QD<br>|
| Experimental: Part 2 - Dose 2<br>Dose 2 will be selected from Part 1 based on the totality of safety, PK, PD and efficacy data from Part 1 will be selected. TERN-701 is planned to be administered once daily. | Drug: TERN-701<br>* TERN-701 orally QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 (RDE) cohorts of TERN-701. | First cycle is 28 days | 
| Part 1 - Serious Adverse Events | Number and percentage of patients with any serious adverse event | up to 3 years | 
| Part 1 - Adverse Events | Number and percentage of patients with any adverse event | up to 3 years | 
| Part 2- Complete Hematologic Response (CHR) | CHR Defined by ELN 2020 criteria in participants who are not in CHR at baseline. | up to 3 years | 
| Part 2: Molecular response (MR) | MR defined by ELN 2020 criteria measured by quantitative polymerase chain reaction of BCR-ABL transcript levels. | up to 3 years | 
| Part 2 - Best categorical shift in BCR-ABL1 transcript levels from baseline | The best categorical molecular response shift on treatment relative to baseline | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CML, allosteric inhibitor of BCR-ABL1, TERN-701, chronic myeloid leukemia, T315I, T315I mutant, CARDINAL, HS-10382