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

A Phase 1 Study of ELVN-001 for the Treatment of Chronic Myeloid Leukemia With and Without T315I Mutation in Japanese Participants

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.

Study Overview

• Status: Recruiting
• Conditions: CML (Chronic Myelogenous Leukemia); Chronic Phase CML
• Intervention / Treatment: Drug: ELVN-001

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 Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuzo Tomonaga; Phone Number: +81-3-6779-8000; Email: ClinicalTrialInformation@cmic.co.jp

Study Locations

• Japan
  • Akita-ken
    • Akita-shi, Akita-ken, Japan
      • Recruiting
      • Akita University Hospital
      • Contact: Yuzo Tomonaga; Phone Number: +81-3-6779-8000
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Recruiting
      • Aiiku Hospital
      • Contact: Yuzo Tomonaga; Phone Number: +81-3-6779-8000
  • Osaka
    • Suita-shi, Osaka, Japan
      • Recruiting
      • The University of Osaka Hospital
      • Contact: Yuzo Tomonaga; Phone Number: +81-3-6779-8000
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan
      • Recruiting
      • Tokyo Medical University Hospital
      • Contact: Yuzo Tomonaga; Phone Number: +81-3-6779-8000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Dose Escalation; ELVN-001 administered in 3+3 dose escalation	Drug: ELVN-001; Orally once or twice daily
Experimental: Part 2 Dose Exploration; 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	Drug: ELVN-001; Orally once or twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Incidence of dose limiting toxicities	DLTs will be used to support that the recommended doses for expansion are </= MTD	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	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	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	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	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	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	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve	PK parameter based on measurement of drug concentration in blood over time	6 months
Maximum concentration	PK parameter based on measurement of drug concentration in blood	6 months
Time of maximum concentration	PK parameter which is the time at which the highest concentration of drug in the blood is measured	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.	6 months
Molecular response (MR)	Measured by quantitative polymerase chain reaction of BCR-ABL transcript levels	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	Up to 3 years
Complete Hematologic Response (CHR)	The proportion of patients who achieve a CHR who are not in CHR at baseline	Up to 3 years

Collaborators and Investigators

• Sponsor: Enliven Therapeutics
• Investigators: Study Director: Helen Collins, MD, Enliven Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): January 22, 2025

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: CML; BCR-ABL; Tyrosine Kinase Inhibitor; T315I; T315I Mutant
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
• Other Study ID Numbers: ELVN-001-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes