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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Myeloid Leukemia; Chronic Myeloid Leukemia, Chronic Phase
• Intervention / Treatment: Drug: TERN-701

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 650-486-9623; Email: clinicaltrials@ternspharma.com

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1- Dose Level 1 of TERN-701; Dose Level 1 of TERN-701 dosed once daily.	Drug: TERN-701; TERN-701 orally QD
Experimental: Part 1- Dose Level 2 of TERN-701; Dose Level 2 of TERN-701 dosed once daily.	Drug: TERN-701; TERN-701 orally QD
Experimental: Part 1- Dose Level 3 of TERN-701; Dose Level 3 of TERN-701 dosed once daily.	Drug: TERN-701; TERN-701 orally QD
Experimental: Part 1- Dose Level 4 of TERN-701; Dose Level 4 of TERN-701 dosed once daily.	Drug: TERN-701; TERN-701 orally QD
Experimental: Part 2 - Dose 1; 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; TERN-701 orally QD
Experimental: Part 2 - Dose 2; 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; TERN-701 orally QD

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Terns, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): December 13, 2023
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 30, 2023
• First Posted (Actual): December 8, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: CML; chronic myeloid leukemia; HS-10382; allosteric inhibitor of BCR-ABL1; TERN-701; T315I; T315I mutant; CARDINAL
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chronic Disease; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: TERN701-1012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No