A Phase 1a/1b Study of ELVN-001 for the Treatment Chronic Myeloid Leukemia

Phase 1RecruitingNCT05304377

Enliven Therapeutics250 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 patients with chronic myeloid leukemia with and without T315I mutations in patients who are relapsed, refractory or intolerant to 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 do not tolerate or benefit from available TKIs.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

250

Conditions

Chronic Myeloid Leukemia Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive Cml

Interventions

ELVN-001DRUG

orally once or twice daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * BCR-ABL1 positive CML in chronic phase, with or without T315I mutation. * US: The patient has failed or is intolerant to at least one prior second-generation tyrosine kinase inhibitor (TKI) or asciminib. Rest of World: The patient has failed, is intolerant to, or not a candidate for, available therapies known to be active for treatment of their CML (country-specific criteria may vary). * ECOG performance status of 0 to 2. * 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 (45)

Outcomes

Primary Outcomes

Phase 1a: Incidence of dose limiting toxicities

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

Time frame: 28 days

Phase 1a: 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

Phase 1a: 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

Phase 1a: 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

Phase 1b: Incidence of adverse events

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

Time frame: up to 3 years

Phase 1b: Incidence of clinically significant laboratory abnormalities

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

Time frame: up to 3 years

Phase 1b: Incidence of clinically significant ECG abnormalities

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

Time frame: up to 3 years

Secondary Outcomes

Central Contacts

Study Contact

CONTACT

707-799-3272 ELVN-001-101@enliventherapeutics.com

Data from ClinicalTrials.gov

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Memorial Sloan Kettering Cancer Center

New York, New York, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, United States

RECRUITING

Oregon Health & Science University-Knight Cardiovascular Institute

Portland, Oregon, United States

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The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

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Royal Adelaide Hospital

Adelaide, Australia

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UZ Gent

Ghent, Belgium

RECRUITING

UZ Leuven

Leuven, Belgium

RECRUITING

CHU Liege

Liège, Belgium

RECRUITING

University Health Network (UHN) - Princess Margaret Cancer Centre

Toronto, Ontario, Canada

RECRUITING

CHU Amiens Picardie Site Sud

Amiens, France

RECRUITING

...and 35 more locations

Phase 1a and 1b: area under the curve

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

Time frame: 6 months

Phase 1a and 1b: maximum concentration

PK parameter based on measurement of drug concentration in blood

Time frame: 6 months

Phase 1a and 1b: 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

Phase 1a and 1b: 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

Phase 1a and 1b: Molecular response (MR)

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

Time frame: up to 3 years

Phase 1b: 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

Phase 1b: 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