ELVN-001 for the Treatment of Chronic Myeloid Leukemia With and Without T315I Mutation in Japanese Participants

Phase 1RecruitingNCT06787144

Enliven Therapeutics21 enrolled

Overview

The purpose of this study is to evaluate the safety, tolerability and determine the recommended dose for further clinical evaluation of ELVN-001 in Japanese patients with chronic phase chronic myeloid leukemia with and without T315I mutations in patients who has failed, or the patient is intolerant to, or not a candidate for, at least 2 prior TKIs.

This first-in-human trial with ELVN-001 is a dose escalation study with the primary purpose to identify the recommended dose(s) for expansion (RDEs) of single agent ELVN-001 in chronic phase CML with or without T315I mutations. The safety, tolerability and pharmacokinetic profile of ELVN-001 will be assessed together with an evaluation of changes in BCR-ABL1 transcript. An understanding of the safety profile, PK and preliminary evidence of anti-CML activity will be used to inform future development of ELVN-001 in adults with CML. By virtue of its predicted pharmacological profile ELVN-001 has the potential to be tolerable and achieve a deep molecular response in patients with CML with or without T315I mutations who have failed, or are intolerant to, or not a candidate for, at least 2 prior TKIs.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

CML (Chronic Myelogenous Leukemia)Chronic Phase CML

Interventions

ELVN-001DRUG

Orally once or twice daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * BCR::ABL1 positive CP-CML that has failed, or the patient is intolerant to, or not a candidate for, at least 2 prior TKIs. * ECOG performance status of 0 to 2. * The patient was born in Japan and both parents and grandparents are Japanese. * Adequate hematologic, hepatic and renal function. * Prior bone marrow transplant allowed if ≥ 6 months prior to the first dose of ELVN-001. Exclusion Criteria: * Treatment with anti-cancer or anti-CML therapy within 7 days or 5 half-lives, whichever is longer. * History of acute tyrosine kinase inhibitor (TKI)-related pancreatitis within 6 months of study entry. Active chronic pancreatitis, or pancreatic disease due to any cause. * QTc \>470 ms.

Locations (4)

Akita University Hospital

Akita, Akita, Japan

RECRUITING

Aiiku Hospital

Sapporo, Hokkaido, Japan

RECRUITING

The University of Osaka Hospital

Suita-shi, Osaka, Japan

RECRUITING

Outcomes

Primary Outcomes

Part 1: Incidence of dose limiting toxicities

DLTs will be used to support that the recommended doses for expansion are \</= MTD

Time frame: 28 days

Part 1: Incidence of adverse events (AEs)

Adverse events will be used to support that the recommended doses for expansion are likely to be tolerable

Time frame: Up to 28 days

Part 1: Incidence of clinically significant laboratory abnormalities

Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable

Time frame: Up to 28 days

Part 1: Incidence of clinically significant ECG abnormalities

Clinically significant ECG abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable

Time frame: Up to 28 days

Part 2: Incidence of adverse events

Adverse events will be used to support that the dose(s) evaluated in exploration is tolerable

Time frame: Up to 3 years

Part 2: Incidence of clinically significant laboratory abnormalities

Clinically significant ECG abnormalities will be used to support that the dose(s) evaluated in exploration is tolerable

Time frame: Up to 3 years

Part 2: Incidence of clinically significant ECG abnormalities

Clinically significant ECG abnormalities will be used to support that the recommended dose(s) evaluated in exploration is tolerable

Time frame: Up to 3 years

Secondary Outcomes

Central Contacts

Yuzo Tomonaga

CONTACT

+81-3-6779-8000 ClinicalTrialInformation@cmic.co.jp

Data from ClinicalTrials.gov

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Area under the curve

PK parameter based on measurement of drug concentration in blood over time

Time frame: 6 months

Maximum concentration

PK parameter based on measurement of drug concentration in blood

Time frame: 6 months

Time of maximum concentration

PK parameter which is the time at which the highest concentration of drug in the blood is measured

Time frame: 6 months

Minimum concentration

PK parameter based on the measurement of the drug concentration that is at the lowest level once steady state has been achieved.

Time frame: 6 months

Molecular response (MR)

Measured by quantitative polymerase chain reaction of BCR-ABL transcript levels

Time frame: Up to 3 years

Duration of Molecular Response

Time from first molecular response (as measured by quantitative polymerase chain reaction of BCR-ABL transcript levels) to loss of response or discontinuation of study drug

Time frame: Up to 3 years

Complete Hematologic Response (CHR)

The proportion of patients who achieve a CHR who are not in CHR at baseline

Time frame: Up to 3 years