A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL)

NCT06163430 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TERN701-1012
• Study Type: interventional
• Target: 180
• Locations: 9 countries
• Sites: 54

Brief Summary

The goal of the study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of TERN-701, a 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 2 recommended dose levels for expansion selected from Part 1. Part 2m (mutation cohort) will further evaluate the efficacy and safety of 500mg of TERN-701 in previously treated CP-CML participants with certain resistance mutations. In both Part 1 and Part 2, participants will receive continuous once 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 (Part 1 only), C1D8, C1D15, and C1D16 (Part 1 only), followed by Day 1 of Cycles 2 through 7, and Day 1 of every 3 cycles thereafter. Approximately 180 participants could be enrolled in this trial, up to 80 participants in Part 1 (dose escalation), including optional backfill cohorts, approximately 80 participants in Part 2 (randomized dose expansion), and approximately 20 participants in Part 2m (mutation cohort). All participants will receive active trial intervention. Four dose-level cohorts have been evaluated in Part 1; two dose levels will be evaluated in Part 2 (Randomized Dose Expansion), and one dose level will be evaluated in Part 2m (mutation cohort).

Conditions

Chronic Myeloid Leukemia; Chronic Myeloid Leukemia, Chronic Phase

Keywords

allosteric inhibitor of BCR-ABL1; CML; TERN-701; chronic myeloid leukemia; T315I; T315I mutant; CARDINAL; HS-10382

Outcome Measures

Primary Outcomes (6)

• 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 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

Study Arms (7)

Part 1- Dose Level 1 (160 mg) of TERN-701

EXPERIMENTAL

Dose Level 1 of TERN-701 dosed once daily.

Drug: TERN-701

Part 1- Dose Level 2 (320 mg) of TERN-701

EXPERIMENTAL

Dose Level 2 of TERN-701 dosed once daily.

Drug: TERN-701

Part 1- Dose Level 3 (400 mg) of TERN-701

EXPERIMENTAL

Dose Level 3 of TERN-701 dosed once daily.

Drug: TERN-701

Part 1- Dose Level 4 (500 mg) of TERN-701

EXPERIMENTAL

Dose Level 4 of TERN-701 dosed once daily.

Drug: TERN-701

Part 2 - Dose 1 (320 mg)

EXPERIMENTAL

Dose 1 was selected based on the totality of safety, PK, PD and efficacy data from Part 1. TERN-701 administered once daily.

Drug: TERN-701

Part 2 - Dose 2 (500 mg)

EXPERIMENTAL

Dose 2 was selected based on the totality of safety, PK, PD and efficacy data from Part 1. TERN-701 administered once daily.

Drug: TERN-701

Part 2m - 500 mg Dose

EXPERIMENTAL

Dose for Part 2m was selected based on the totality of safety, PK, PD and efficacy data from Part 1 and nonclinical data. TERN-701 is administered once daily.

Drug: TERN-701

Interventions

TERN-701 DRUG

TERN-701 orally QD

Part 1- Dose Level 1 (160 mg) of TERN-701; Part 1- Dose Level 2 (320 mg) of TERN-701; Part 1- Dose Level 3 (400 mg) of TERN-701; Part 1- Dose Level 4 (500 mg) of TERN-701; Part 2 - Dose 1 (320 mg); Part 2 - Dose 2 (500 mg); Part 2m - 500 mg Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 at least one prior TKI and have treatment failure, suboptimal response, or treatment intolerance
• Prior treatment with asciminib is allowed
• Adequate organ function, as assessed by local laboratory

You may not qualify if:

• 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)

Sponsors & Collaborators

• Terns, Inc.: lead

Study Sites (54)

University of Alabama Medicine (UAB Medicine)

Birmingham, Alabama, 35233, United States

RECRUITING

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

UC Irvine Health

Orange, California, 92868, United States

RECRUITING

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado, 80303, United States

RECRUITING

Florida Cancer Specialists - South Region Research Office

Fort Myers, Florida, 33901, United States

NOT YET RECRUITING

Florida Cancer Affiliates - Ocala

Ocala, Florida, 34474, United States

RECRUITING

Florida Cancer Specialists - North Region Research Office

St. Petersburg, Florida, 33705, United States

NOT YET RECRUITING

Florida Cancer Specialists - East Region Research Office

West Palm Beach, Florida, 33401, United States

NOT YET RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - Main Campus

New York, New York, 10065, United States

RECRUITING

Atrium Health Levine Cancer Institute

Winston-Salem, North Carolina, 27103, United States

RECRUITING

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Thomas Jefferson University - Center City (Philadelphia)

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Tristar BMT

Nashville, Tennessee, 37203, United States

RECRUITING

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Monash Medical Centre

Clayton, Victoria, 3168, Australia

NOT YET RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

NOT YET RECRUITING

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

RECRUITING

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, 69008, France

RECRUITING

Institut Bergonié

Bordeaux, 33076, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13273, France

RECRUITING

CHU de Nantes (University Hospital of Nantes) - Hôtel Dieu

Nantes, 44093, France

RECRUITING

Hôpital Saint Louis

Paris, 75010, France

RECRUITING

Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

RECRUITING

Universitätsklinikum Aachen

Aachen, 52074, Germany

RECRUITING

Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin

Berlin, 10117, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

Universitätsklinikum Jena

Jena, 07747, Germany

RECRUITING

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

RECRUITING

Klinikum rechts der lsar der Technischen Universität München

München, 81675, Germany

RECRUITING

Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola

Bologna, 40138, Italy

RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori - SC Centro di Ricerca Fase I

Monza, 20900, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, 20900, Italy

RECRUITING

Auckland City Hospital

Auckland, 1023, New Zealand

NOT YET RECRUITING

Christchurch Hospital

Christchurch, 8011, New Zealand

RECRUITING

Uijeorigbu Eulji Medical Center, Eulji University

Uijeongbu-si, Gyeonggi-do, 11749, South Korea

RECRUITING

Hallym University Sacred Heart Hospital

Anyang-si, Gyeonggido, 14068, South Korea

RECRUITING

Dong-A University hospital

Busan, 49201, South Korea

RECRUITING

Keimyung University Dongsan Hospital

Daegu, 42601, South Korea

RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital Universitari Germans Trias i Pujol (ICO Badalona)

Barcelona, 08916, Spain

RECRUITING

Hospital Universitario de Gran Canaria Doctor Negrín

Las Palmas, 35010, Spain

RECRUITING

Hospital Universitario de La Princesa

Madrid, 28006, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital de Día Quirónsalud Zaragoza

Zaragoza, 50012, Spain

RECRUITING

Imperial College Healthcare NHS Trust

London, England, W12 0HS, United Kingdom

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Study Director

CONTACT

650-525-5535; clinicaltrials@ternspharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A sequential Intervention Model was used for Part 1 Dose Escalation. In the Part 2 Randomized Dose Expansion, participants will be randomized to one of two selected doses in parallel for the duration of the study. Participants enrolled into Part 2m (mutational cohort) will receive the same selected dose

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: December 8, 2023
• Study Start: March 26, 2024
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): May 31, 2030
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); FR (6); DE (7); NZ (2); IT (4); ES (8); KR (4); GB (1); US (18)