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

Официальное название

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

Обзор

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).

Вмешательства

• Препарат TERN-701
  TERN-701 orally QD

Первичные конечные точки

• Part 1 - Incidence of Dose Limiting Toxicities during the first cycle of treatment [Срок оценки: First cycle is 28 days]
• Part 1 - Serious Adverse Events [Срок оценки: up to 3 years]
• Part 1 - Adverse Events [Срок оценки: up to 3 years]
• Part 2- Complete Hematologic Response (CHR) [Срок оценки: up to 3 years]
• Part 2: Molecular response (MR) [Срок оценки: up to 3 years]
• Part 2 - Best categorical shift in BCR-ABL1 transcript levels from baseline [Срок оценки: up to 3 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 18 центров

• University of Alabama Medicine (UAB Medicine) — Birmingham
• Banner MD Anderson Cancer Center — Gilbert
• UC Irvine Health — Orange
• Rocky Mountain Cancer Centers, LLP — Lone Tree
• Florida Cancer Specialists - South Region Research Office — Fort Myers
• Florida Cancer Affiliates - Ocala — Ocala
• Florida Cancer Specialists - North Region Research Office — St. Petersburg
• Florida Cancer Specialists - East Region Research Office — West Palm Beach
• … и ещё 10 центров

Испания · 8 центров

• Hospital Universitari Vall d'Hebrón — Barcelona
• Hospital Clínic de Barcelona — Barcelona
• Hospital Universitari Germans Trias i Pujol (ICO Badalona) — Barcelona
• Hospital Universitario de Gran Canaria Doctor Negrín — Las Palmas
• Hospital Universitario de La Princesa — Madrid
• Hospital Universitario Ramón y Cajal — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital de Día Quirónsalud Zaragoza — Zaragoza

Германия · 7 центров

• Universitätsklinikum Aachen — Aachen
• Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin — Berlin
• Universitätsklinikum Frankfurt — Frankfurt am Main
• Medizinische Hochschule Hannover — Hanover
• Universitätsklinikum Jena — Jena
• Universitätsklinikum Mannheim — Mannheim
• Klinikum rechts der lsar der Technischen Universität München — München

Франция · 6 центров

• Centre Léon Bérard — Lyon
• Institut Bergonié — Bordeaux
• Institut Paoli Calmettes — Marseille
• CHU de Nantes (University Hospital of Nantes) - Hôtel Dieu — Nantes
• Hôpital Saint Louis — Paris
• Centre Hospitalier Lyon-Sud — Pierre-Bénite

Австралия · 4 центра

• Royal Adelaide Hospital — Adelaide
• Monash Medical Centre — Clayton
• Peter MacCallum Cancer Centre — Melbourne
• Royal Perth Hospital — Perth

Италия · 4 центра

• Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola — Bologna
• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan
• Fondazione IRCCS San Gerardo dei Tintori - SC Centro di Ricerca Fase I — Monza
• Fondazione IRCCS San Gerardo dei Tintori — Monza

South Korea · 4 центра

• Uijeorigbu Eulji Medical Center, Eulji University — Uijeongbu-si
• Hallym University Sacred Heart Hospital — Anyang-si
• Dong-A University hospital — Busan
• Keimyung University Dongsan Hospital — Daegu

Новая Зеландия · 2 центра

• Auckland City Hospital — Auckland
• Christchurch Hospital — Christchurch

Великобритания · 1 центр

• Imperial College Healthcare NHS Trust — London

Идентификаторы

NCT: NCT06163430 · TERN701-1012

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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