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

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ClinicalTrials.gov Identifier: NCT05304377
Recruitment Status : Recruiting
First Posted : March 31, 2022
Last Update Posted : April 9, 2024
Sponsor:
Information provided by (Responsible Party):
Enliven Therapeutics

Study Description
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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 patients with chronic myeloid leukemia with and without T315I mutations in patients who are relapsed, refractory or intolerant to TKIs.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: ELVN-001 Phase 1

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 do not tolerate or benefit from available TKIs.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1a/1b Study of ELVN-001 for the Treatment of Chronic Myeloid Leukemia
Actual Study Start Date : May 22, 2022
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1a Dose Escalation
ELVN-001 administered in 3+3 dose escalation
 Drug: ELVN-001
orally once or twice daily
Experimental: Phase 1b Dose Expansion at recommended dose level 1
ELVN-001 administered at the recommended dose in CML without T315I mutations
 Drug: ELVN-001
orally once or twice daily
Experimental: Phase 1b Dose Expansion at recommended dose level 2
ELVN-001 administered at a different recommended dose in CML without T315I mutations
 Drug: ELVN-001
orally once or twice daily
Experimental: Phase 1b expansion arm in T315I mutated CML
ELVN-001 administered at the recommended dose for CML with T315I mutation
 Drug: ELVN-001
orally once or twice daily


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1a: Incidence of dose limiting toxicities [ Time Frame: 28 days ]
    DLTs will be used to support that the recommended doses for expansion are </= MTD

  2. Phase 1a: Incidence of adverse events (AEs) [ Time Frame: up to 28 days ]
    Adverse events will be used to support that the recommended doses for expansion are likely to be tolerable

  3. Phase 1a: Incidence of clinically significant laboratory abnormalities [ Time Frame: up to 28 days ]
    Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable

  4. Phase 1a: Incidence of clinically significant ECG abnormalities [ Time Frame: up to 28 days ]
    Clinically significant ECG abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable

  5. Phase 1b: Incidence of adverse events [ Time Frame: up to 3 years ]
    Adverse events will be used to support that the dose(s) evaluated in expansion is tolerable

  6. Phase 1b: Incidence of clinically significant laboratory abnormalities [ Time Frame: up to 3 years ]
    Clinically significant ECG abnormalities will be used to support that the dose(s) evaluated in expansion is tolerable

  7. Phase 1b: Incidence of clinically significant ECG abnormalities [ Time Frame: up to 3 years ]
    Clinically significant ECG abnormalities will be used to support that the recommended dose(s) evaluated in expansion is tolerable


Secondary Outcome Measures :
  1. Phase 1a and 1b: area under the curve [ Time Frame: 6 months ]
    PK parameter based on measurement of drug concentration in blood over time

  2. Phase 1a and 1b: maximum concentration [ Time Frame: 6 months ]
    PK parameter based on measurement of drug concentration in blood

  3. Phase 1a and 1b: time of maximum concentration [ Time Frame: 6 months ]
    PK parameter which is the time at which the highest concentration of drug in the blood is measured

  4. Phase 1a and 1b: minimum concentration [ Time Frame: 6 months ]
    PK parameter based on the measurement of the drug concentration that is at the lowest level once steady state has been achieved.

  5. Phase 1a and 1b: Molecular response (MR) [ Time Frame: up to 3 years ]
    measured by quantitative polymerase chain reaction of BCR-ABL transcript levels

  6. Phase 1b: Duration of Molecular Response [ Time Frame: 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

  7. Phase 1b: Complete Hematologic Response (CHR) [ Time Frame: up to 3 years ]
    The proportion of patients who achieve a CHR who are not in CHR at baseline


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • BCR-ABL1 positive CML in chronic phase, with or without T315I mutation.
  • The patient has failed, is intolerant to, or not a candidate for, available therapies known to be active for treatment of their CML.
  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05304377


Contacts
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Contact: Study Contact 707-799-3272 ELVN-001-101@enliventherapeutics.com

Locations
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Sponsors and Collaborators
Enliven Therapeutics
More Information
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Responsible Party: Enliven Therapeutics
ClinicalTrials.gov Identifier: NCT05304377    
Other Study ID Numbers: ELVN-001-101
First Posted: March 31, 2022    Key Record Dates
Last Update Posted: April 9, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Enliven Therapeutics:
CML
Tyrosine kinase inhibitor
T315I
T315I mutant
BCR-ABL
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
 Myeloproliferative Disorders
Bone Marrow Diseases
Chronic Disease
Disease Attributes
Pathologic Processes