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; Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive; 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 do not tolerate or benefit from available TKIs.

• Study Type: Interventional
• Enrollment (Estimated): 250
• 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
• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • UZ Gent
    • Contact: Dominiek Mazure, Dr.; Phone Number: +32 9 332 21 11
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Peter Vandenberghe, Dr.; Phone Number: +32 16 33 22 11
  • Liège, Belgium, 4000
    • Recruiting
    • Chu Liege
    • Contact: Marie Lejeune, Dr.; Phone Number: +32 4 323 00 00
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • University Health Network (Uhn) - Princess Margaret Cancer Centre
      • Contact: Dong Hwan Dennis Kim, Dr; Phone Number: 2464 +1 416 946 4501
• France
  • Amiens, France, 80054
    • Recruiting
    • CHU Amiens Picardie Site Sud
    • Contact: Amandine Charbonnier, Dr; Phone Number: +33 322455914
  • 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
  • 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: +33 478782737
  • Pierre-Bénite, France, 69495
    • Withdrawn
    • Centre Hospitalier Lyon Sud
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Uniklinik RWTH Aachen Medizinische
    • Contact: Martina Crysandt, Dr; Phone Number: +49 241 8080862
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Campus Virchow
    • Contact: Philipp Le Coutre, Dr; Phone Number: +49 30 450 665 307
  • Frankfurt, Germany, 60596
    • Recruiting
    • Klinikum der Goethe Universitat
    • Contact: Fabian Lang, Dr; Phone Number: +49 821 4861274
  • Homburg, Germany, 66421
    • Recruiting
    • Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes
    • Contact: Sarah Altmeyer, Dr; Phone Number: +49 68411615001
  • Jena, Germany, 07747
    • Recruiting
    • Universitaetsklinikum Jena
    • Contact: Andreas Hochhaus, Prof Dr; Phone Number: +49 3641 934200
  • Mannheim, Germany, 68167
    • Recruiting
    • Medizinische Universitatsklinik Mannheim der Universitat Heidelberg
    • Contact: Susanne Saussele, Prof Dr; Phone Number: +49 621 383 6966
  • Rostock, Germany, 18057
    • Recruiting
    • Universitaetsmedizin Rostock
    • Contact: Christian Junghanss, Dr; Phone Number: +49 3814947421
• Hungary
  • Budapest, Hungary, 1083
    • Recruiting
    • Semmelweis Egyetem, Belgyogyaszati es Onkologiai Klinika
    • Contact: Istvan Tackas MD; Phone Number: +36 1 459 1500
  • Pécs, Hungary, 7624
    • Recruiting
    • Pecsi Tudomanyegyetem Klinikai Kozpont (University of Pecs, Clinical Centre)
    • Contact: Hussain Alizadeh, Dr; Phone Number: +36 72 501 500
• Israel
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center
    • Contact: David Lavie, Dr.; Phone Number: +972 02-6779267
  • Nahariya, Israel, 2210001
    • Recruiting
    • The Galilee Medical Center
    • Contact: Galia Stemer, Dr.; Phone Number: +972 04-9107301
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin Medical Center
    • Contact: Adi Shacham-Abulafia, Dr.; Phone Number: +972 03-9377909
• Italy
  • Ancona, Italy, 60126
    • Recruiting
    • Azienda Ospedaliero Universitaria delle Marche
    • Contact: Erika Morsia, Dr.; Phone Number: +39 071 5961
• Netherlands
  • Nijmegen, Netherlands, 6525
    • Recruiting
    • Radboud University Medical Center
    • Contact: N.M.A. Blijlevens, Dr.; Phone Number: +31 (0)24 361 11 11
• Poland
  • Nowy Sącz, Poland, 33-300
    • Recruiting
    • Szpital Specjalistycnzy im. Jedrzeja Sniadeckiego w Nowym Saczu
    • Contact: Szymon Fornagiel, Dr; Phone Number: +48 18 443 88 77
  • Torun, Poland, 87-100
    • Recruiting
    • MICS Centrum Medyczne Torun
    • Contact: Dominik Chraniuk, Dr.; Phone Number: +48 662 062 410
  • Warsaw, Poland, 02-776
    • Recruiting
    • Instytut Hematologii I Transfuzjologii
    • Contact: Ewa Lech-Maranda, Dr.; Phone Number: +48 22 349 61 00
• South Korea
  • Daegu, South Korea, 42601
    • Withdrawn
    • Keimyung University Dongsan Hospital
  • Gyeonggi-do, South Korea, 11749
    • Recruiting
    • Uijeongbu Eulji Medical Center
    • Contact: Dong-Wook Kim, Dr; Phone Number: +82 3118990001
  • Hwasun, South Korea, 58128
    • Withdrawn
    • Chonnam National University Hwasun Hospital
  • Seoul, South Korea, 06351
    • Withdrawn
    • Samsung Medical Center
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, South Korea, 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
    • Terminated
    • Complejo Hospitalario de Toledo - Hospital Virgen de la Salud
  • 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 Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • Beatson West of Scotland Cancer Centre, Gartnavel General Hospital
    • Contact: Mhairi Copland, Dr; Phone Number: +44 141 301 7000
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Hammersmith Hospital Imperial College Healthcare NHS Trust
    • Contact: Dragana Milojkovic, Dr.; Phone Number: +44 20 3313 8335
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
    • Contact: John Chadwick, Dr; Phone Number: +44 (0) 161 446 3000
• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Michael Mauro, MD; Phone Number: +1 347 798 9213
    • The Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
      • Contact: David Levitz MD; Phone Number: 718-920-4321
  • 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: Fadi Haddad, 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.
• 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.

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

3

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 (non-T315I); ELVN-001 administered at one or more recommended dose(s) for expansion in CML without T315I mutations	Drug: ELVN-001; orally once or twice daily
Experimental: Phase 1b expansion (T315I); ELVN-001 administered at the recommended dose for expansion 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, 2027
• Study Completion (Estimated): December 1, 2027

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 1, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: CML; ENABLE; BCR-ABL; Tyrosine kinase inhibitor; T315I; T315I mutant; active site inhibitor of BCR-ABL
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Myeloproliferative Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
• 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
• product manufactured in and exported from the U.S.: No