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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Myeloid Leukemia
• 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 do not tolerate or benefit from available TKIs.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 707-799-3272; Email: ELVN-001-101@enliventherapeutics.com

Study Locations

• Australia
  • Adelaide, Australia, SA 5000
    • Recruiting
    • Royal Adelaide Hospital
    • Contact: Naranie Shanmuganathan, Dr; Phone Number: +61 8 7074 0000
• France
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
    • Contact: Gabriel Etienne, Dr; Phone Number: +33 5 56 33 33 33
  • Le Chesnay, France, 78157
    • Withdrawn
    • Centre Hospitalier de Versailles (CHV)
  • Lille, France, 59000
    • Recruiting
    • CHRU de Lille - Hopital Calmette-Boulevard du Pr Leclercq CHRU Lille
    • Contact: Valerie Coiteux, Dr; Phone Number: +33 3 20 44 59 62
  • Limoges, France, 87000
    • Recruiting
    • Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
    • Contact: Pascal Turlure, Dr; Phone Number: +33 5 55 05 55 55
  • Lyon, France, 69008
    • Recruiting
    • Centre Leon Berard
    • Contact: Franck Nicolini, Dr; Phone Number: +04 78 78 28 28
  • Pierre Benite Cedex, France, 69495
    • Recruiting
    • Centre Hospitalier Lyon Sud
    • Contact: Marie Balsat, Dr; Phone Number: +33 825 08 25 69
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Uniklinik RWTH Aachen Medizinische Klinik III
    • Contact: Martina Crysandt, Dr Med; Phone Number: +49 241 8080862
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Campus Virchow
    • Contact: Philipp Le Coutre, Dr; Phone Number: +49 30 45050
  • Frankfurt, Germany, 60596
    • Recruiting
    • Klinikum der Goethe Universitat
    • Contact: Fabian Lang, Dr Med; Phone Number: +49 821 4861274
  • Jena, Germany, 07747
    • Recruiting
    • Universitaetsklinikum Jena
    • Contact: Andreas Hochhaus, Prof Dr; Phone Number: +49 3641 9300
  • Mannheim, Germany, 68167
    • Recruiting
    • Medizinische Universitatsklinik Mannheim der Universitat Heidelberg
    • Contact: Susanne Saussele, Prof Dr; Phone Number: +49 621 3830
• Korea, Republic of
  • Daegu, Korea, Republic of, 42601
    • Withdrawn
    • Keimyung University Dongsan Hospital
  • Gyeonggi-do, Korea, Republic of, 11749
    • Recruiting
    • Uijeongbu Eulji Medical Center
    • Contact: Dong-Wook Kim, Dr; Phone Number: +82 31-1899-0001
  • Hwasun, Korea, Republic of, 58128
    • Withdrawn
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 06351
    • Withdrawn
    • Samsung Medical Center
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, Korea, Republic of, 54907
      • Withdrawn
      • Chonbuk National University Hospital
• Spain
  • Barcelona, Spain, 08003
    • Recruiting
    • Hospital Del Mar
    • Contact: Patricia Velez Tenza, Dr; Phone Number: +34 932 48 30 00
  • Las Palmas De Gran Canaria, Spain, 35010
    • Withdrawn
    • Hospital Universitario de Gran Canaria Dr. Negrin, Servicio Canario e Salud (SCS)
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Maria Raquel de Paz Arias, Dr; Phone Number: +34 917 27 70 00
  • Toledo, Spain, 45007
    • Recruiting
    • Complejo Hospitalario de Toledo - Hospital Virgen de la Salud
    • Contact: Luis Felipe Casado Montero, Dr; Phone Number: +34 925 39 68 90
  • Valencia, Spain, 46026
    • Recruiting
    • Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
    • Contact: Elvira Mora Castera, Dr; Phone Number: +34 961 24 40 00
• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Michael Mauro, MD; Phone Number: 347-798-9213
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University-Knight Cardiovascular Institute
      • Contact: Michael Heinrich, MD; Phone Number: 503-418-1964
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Koji Sasaki, MD; Phone Number: 877-632-6789

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a: Incidence of dose limiting toxicities	DLTs will be used to support that the recommended doses for expansion are </= MTD	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	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	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	up to 28 days
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	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	up to 3 years
Phase 1b: Incidence of adverse events	Adverse events will be used to support that the dose(s) evaluated in expansion is tolerable	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a and 1b: area under the curve	PK parameter based on measurement of drug concentration in blood over time	6 months
Phase 1a and 1b: maximum concentration	PK parameter based on measurement of drug concentration in blood	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	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.	6 months
Phase 1a and 1b: Molecular response (MR)	measured by quantitative polymerase chain reaction of BCR-ABL transcript levels	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	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	up to 3 years

Collaborators and Investigators

• Sponsor: Enliven Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CML; BCR-ABL; Tyrosine kinase inhibitor; T315I; T315I mutant
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chronic Disease; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: ELVN-001-101

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