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

Terns Pharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Chronic Myeloid Leukemia; Chronic Myeloid Leukemia, Chronic Phase

Treatments: Drug: TERN-701

Study type: Interventional

Funder types: Industry

Identifiers

NCT06163430

TERN701-1012

Details and patient eligibility

About

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 100 participants could be enrolled in this trial, including up to 60 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.

At least 4 dose-level cohorts may be evaluated in Part 1; at least 2 dose levels may be evaluated in Part 2.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 active site targeting TKIs and have treatment failure, suboptimal response, or treatment intolerance
• Prior treatment with asciminib may be 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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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100 participants in 6 patient groups

Part 1- Dose Level 1 of TERN-701

Experimental group

Description:

Dose Level 1 of TERN-701 dosed once daily.

Treatment:

Drug: TERN-701

Part 1- Dose Level 2 of TERN-701

Experimental group

Description:

Dose Level 2 of TERN-701 dosed once daily.

Treatment:

Drug: TERN-701

Part 1- Dose Level 3 of TERN-701

Experimental group

Description:

Dose Level 3 of TERN-701 dosed once daily.

Treatment:

Drug: TERN-701

Part 1- Dose Level 4 of TERN-701

Experimental group

Description:

Dose Level 4 of TERN-701 dosed once daily.

Treatment:

Drug: TERN-701

Part 2 - Dose 1

Experimental group

Description:

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.

Treatment:

Drug: TERN-701

Part 2 - Dose 2

Experimental group

Description:

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.

Treatment:

Drug: TERN-701