Clinical trial NCT06163430: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Chronic Myeloid Leukemia, Chronic Phase
Chronic Myeloid Leukemia
Keywords: allosteric inhibitor of BCR-ABL1
CML
TERN-701
chronic myeloid leukemia
T315I
T315I mutant
CARDINAL
HS-10382
Lead sponsor: Terns, Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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
* 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)

Primary outcomes:
measure: Part 1 - Incidence of Dose Limiting Toxicities during the first cycle of treatment
timeFrame: First cycle is 28 days
measure: Part 1 - Serious Adverse Events
timeFrame: up to 3 years
measure: Part 1 - Adverse Events
timeFrame: up to 3 years
measure: Part 2- Complete Hematologic Response (CHR)
timeFrame: up to 3 years
measure: Part 2: Molecular response (MR)
timeFrame: up to 3 years
measure: Part 2 - Best categorical shift in BCR-ABL1 transcript levels from baseline
timeFrame: up to 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - Main Campus
state: New York
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Nashville
country: United States
facility: Tristar BMT
state: Tennessee
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Bordeaux
country: France
facility: Institut Bergonié
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Nantes Cedex 1
country: France
facility: CHU de Nantes (University Hospital of Nantes) - Hôtel Dieu
city: Paris
country: France
facility: Hôpital Saint Louis
city: Pierre-Benite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Jena
country: Germany
facility: Apotheke des Universitätsklinikums Jena
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: München
country: Germany
facility: Klinikum rechts der lsar der Technischen Universität München
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - SC Farmacia
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori - SC Centro di Ricerca Fase I
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori
city: Uijeongbu-si
country: Korea, Republic of
facility: Uijeorigbu Eulji Medical Center, Eulji University
state: Gyeonggi-do
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Gyeonggido
city: Busan
country: Korea, Republic of
facility: Dong-A University hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol (ICO Badalona)
city: Las Palmas
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrín
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Zaragoza
country: Spain
facility: Hospital Quirónsalud Zaragoza
city: Zaragoza
country: Spain
facility: Hospital de Día Quirónsalud Zaragoza
Study officials:
References: