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

Phase 1

Recruiting

• Conditions: Chronic Myeloid Leukemia, Chronic Phase; Chronic Myeloid Leukemia
• Interventions: Drug: TERN-701

• Registration Number: NCT06163430
• Lead Sponsor: Terns, Inc.

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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-08
• Study First Submitted QC: 2023-11-30
• Study First Posted: 2023-12-08
• Study Start: 2024-03-26
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-23
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-11-30
• Study Completion: 2026-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1- Dose Level 1 of TERN-701	TERN-701	Dose Level 1 of TERN-701 dosed once daily.
Part 1- Dose Level 3 of TERN-701	TERN-701	Dose Level 3 of TERN-701 dosed once daily.
Part 1- Dose Level 2 of TERN-701	TERN-701	Dose Level 2 of TERN-701 dosed once daily.
Part 2 - Dose 1	TERN-701	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.
Part 2 - Dose 2	TERN-701	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.
Part 1- Dose Level 4 of TERN-701	TERN-701	Dose Level 4 of TERN-701 dosed once daily.

Primary Outcome Measures

Name	Time	Method
Part 1 - Serious Adverse Events	up to 3 years	Number and percentage of patients with any serious adverse event
Part 2 - Best categorical shift in BCR-ABL1 transcript levels from baseline	up to 3 years	The best categorical molecular response shift on treatment relative to baseline
Part 1 - Incidence of Dose Limiting Toxicities during the first cycle of treatment	First cycle is 28 days	Determination of the Maximum Tolerated Dose (MTD) and recommended doses for expansion (RDE) cohorts of TERN-701.
Part 2- Complete Hematologic Response (CHR)	up to 3 years	CHR Defined by ELN 2020 criteria in participants who are not in CHR at baseline.
Part 2: Molecular response (MR)	up to 3 years	MR defined by ELN 2020 criteria measured by quantitative polymerase chain reaction of BCR-ABL transcript levels.
Part 1 - Adverse Events	up to 3 years	Number and percentage of patients with any adverse event

Trial Locations

Locations (40)

UC Irvine Health; 🇺🇸 Orange, California, United States

Rocky Mountain Cancer Centers, LLP; 🇺🇸 Lone Tree, Colorado, United States

Georgia Cancer Center at Augusta University; 🇺🇸 Augusta, Georgia, United States

Memorial Sloan Kettering Cancer Center - Main Campus; 🇺🇸 New York, New York, United States

Willamette Valley Cancer Institute and Research Center; 🇺🇸 Eugene, Oregon, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Tristar BMT; 🇺🇸 Nashville, Tennessee, United States

The University of Texas M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Royal Perth Hospital; 🇦🇺 Perth, Western Australia, Australia

Institut Bergonié; 🇫🇷 Bordeaux, France

Institut Paoli Calmettes; 🇫🇷 Marseille Cedex 9, France

CHU de Nantes (University Hospital of Nantes) - Hôtel Dieu; 🇫🇷 Nantes Cedex 1, France

Hôpital Saint Louis; 🇫🇷 Paris, France

Centre Hospitalier Lyon-Sud; 🇫🇷 Pierre-Benite, France

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Apotheke des Universitätsklinikums Jena; 🇩🇪 Jena, Germany

Universitätsklinikum Jena; 🇩🇪 Jena, Germany

Universitätsklinikum Mannheim; 🇩🇪 Mannheim, Germany

Klinikum rechts der lsar der Technischen Universität München; 🇩🇪 München, Germany

Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola; 🇮🇹 Bologna, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - SC Farmacia; 🇮🇹 Milano, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; 🇮🇹 Milano, Italy

Fondazione IRCCS San Gerardo dei Tintori - SC Centro di Ricerca Fase I; 🇮🇹 Monza, Italy

Fondazione IRCCS San Gerardo dei Tintori; 🇮🇹 Monza, Italy

Uijeorigbu Eulji Medical Center, Eulji University; 🇰🇷 Uijeongbu-si, Gyeonggi-do, Korea, Republic of

Hallym University Sacred Heart Hospital; 🇰🇷 Anyang-si, Gyeonggido, Korea, Republic of

Dong-A University hospital; 🇰🇷 Busan, Korea, Republic of

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital de Día Quirónsalud Zaragoza; 🇪🇸 Zaragoza, Spain

Keimyung University Dongsan Hospital; 🇰🇷 Daegu, Korea, Republic of

Hospital Quirónsalud Zaragoza; 🇪🇸 Zaragoza, Spain

Hospital Universitari Vall d'Hebrón; 🇪🇸 Barcelona, Spain

Hospital Universitari Germans Trias i Pujol (ICO Badalona); 🇪🇸 Barcelona, Spain

Hospital Universitario de Gran Canaria Doctor Negrín; 🇪🇸 Las Palmas, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario de La Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain