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

Phase 1

Recruiting

• Conditions: CML (Chronic Myelogenous Leukemia); Chronic Phase CML
• Interventions: Drug: ELVN-001

• Registration Number: NCT06787144
• Lead Sponsor: Enliven Therapeutics

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2024-12-16
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-16
• Study First Posted: 2025-01-22
• Study Start: 2025-01-23
• Last Update Submitted: 2025-01-28
• Last Update Posted: 2025-01-29
• Primary Completion: 2028-01
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 21

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 Dose Escalation	ELVN-001	ELVN-001 administered in 3+3 dose escalation
Part 2 Dose Exploration	ELVN-001	ELVN-001 administered to approximately 6 participants per dose level who may be enrolled at or below the dose levels that have been deemed safe and tolerable in Part 1

Primary Outcome Measures

Name	Time	Method
Part 1: Incidence of dose limiting toxicities	28 days	DLTs will be used to support that the recommended doses for expansion are \</= MTD
Part 1: Incidence of adverse events (AEs)	Up to 28 days	Adverse events will be used to support that the recommended doses for expansion are likely to be tolerable
Part 1: Incidence of clinically significant laboratory abnormalities	Up to 28 days	Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Part 1: Incidence of clinically significant ECG abnormalities	Up to 28 days	Clinically significant ECG abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Part 2: Incidence of adverse events	Up to 3 years	Adverse events will be used to support that the dose(s) evaluated in exploration is tolerable
Part 2: Incidence of clinically significant laboratory abnormalities	Up to 3 years	Clinically significant ECG abnormalities will be used to support that the dose(s) evaluated in exploration is tolerable
Part 2: Incidence of clinically significant ECG abnormalities	Up to 3 years	Clinically significant ECG abnormalities will be used to support that the recommended dose(s) evaluated in exploration is tolerable

Secondary Outcome Measures

Name	Time	Method
Time of maximum concentration	6 months	PK parameter which is the time at which the highest concentration of drug in the blood is measured
Minimum concentration	6 months	PK parameter based on the measurement of the drug concentration that is at the lowest level once steady state has been achieved.
Area under the curve	6 months	PK parameter based on measurement of drug concentration in blood over time
Maximum concentration	6 months	PK parameter based on measurement of drug concentration in blood
Molecular response (MR)	Up to 3 years	Measured by quantitative polymerase chain reaction of BCR-ABL transcript levels
Duration of Molecular Response	Up to 3 years	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
Complete Hematologic Response (CHR)	Up to 3 years	The proportion of patients who achieve a CHR who are not in CHR at baseline

Trial Locations

Locations (4)

Akita University Hospital; 🇯🇵 Akita-shi, Akita-ken, Japan

Aiiku Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Osaka University Hospital; 🇯🇵 Suita-shi, Osaka, Japan

Tokyo Medical University Hospital; 🇯🇵 Shinjuku-ku, Tokyo, Japan