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

• ClinicalTrials.gov Identifier: NCT06163430
• Recruitment Status: Not yet recruiting
• First Posted: December 8, 2023
• Last Update Posted: December 8, 2023
• Sponsor: Terns, Inc.
• Information provided by (Responsible Party): Terns, Inc.

Tracking Information

• First Submitted Date: November 8, 2023
• First Posted Date: December 8, 2023
• Last Update Posted Date: December 8, 2023
• Estimated Study Start Date: December 13, 2023
• Estimated Primary Completion Date: November 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2023)

• Part 1 - Incidence of Dose Limiting Toxicities during the first cycle of treatment [ Time Frame: First cycle is 28 days ]
  Determination of the Maximum Tolerated Dose (MTD) and recommended doses for expansion (RDE) cohorts of TERN-701.
• Part 1 - Serious Adverse Events [ Time Frame: up to 3 years ]
  Number and percentage of patients with any serious adverse event
• Part 1 - Adverse Events [ Time Frame: up to 3 years ]
  Number and percentage of patients with any adverse event
• Part 2- Complete Hematologic Response (CHR) [ Time Frame: up to 3 years ]
  CHR Defined by ELN 2020 criteria in participants who are not in CHR at baseline.
• Part 2: Molecular response (MR) [ Time Frame: 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 [ Time Frame: up to 3 years ]
  The best categorical molecular response shift on treatment relative to baseline

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Myeloid Leukemia, Chronic Phase
• Chronic Myeloid Leukemia

Intervention

Drug: TERN-701

TERN-701 orally QD

Study Arms

• Experimental: Part 1- Dose Level 1 of TERN-701
  Dose Level 1 of TERN-701 dosed once daily.
  Intervention: Drug: TERN-701
• Experimental: Part 1- Dose Level 2 of TERN-701
  Dose Level 2 of TERN-701 dosed once daily.
  Intervention: Drug: TERN-701
• Experimental: Part 1- Dose Level 3 of TERN-701
  Dose Level 3 of TERN-701 dosed once daily.
  Intervention: Drug: TERN-701
• Experimental: Part 1- Dose Level 4 of TERN-701
  Dose Level 4 of TERN-701 dosed once daily.
  Intervention: Drug: TERN-701
• 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.
  Intervention: Drug: TERN-701
• 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.
  Intervention: Drug: TERN-701

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: November 30, 2023): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2026
• Estimated Primary Completion Date: November 30, 2025 (Final data collection date for primary outcome measure)

Eligibility 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 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Director; 650-486-9623; clinicaltrials@ternspharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06163430
• Other Study ID Numbers: TERN701-1012
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Terns, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Terns, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Terns, Inc.
• Verification Date: November 2023