Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research, CML, Chronic Myeloid Malignancies, drug development, Diseases, Therapies, Myeloid Malignancies
Non-clinical data suggests ELVN-001 has a favorable absorption, distribution, metabolism, elimination and a pharmacokinetic (PK) profile supporting once daily (QD) dosing, low risk of QTc prolongation, and potential to avoid drug-drug interactions, particularly CYP-mediated. This first-in-human (FIH) study will evaluate the safety, tolerability, PK and preliminary anti-CML activity of ELVN-001 in patients (pts) with chronic (CP) or accelerated phase CML with and without T315I mutations.
Objectives: The primary objectives are to determine the recommended doses for expansion (RDE) and to evaluate the safety and tolerability of ELVN-001. Secondary objectives are to assess the PK profile and preliminary efficacy.
Design: A phase 1 open-label, multi-center, dose escalation and expansion study. Eligible pts are adults with CP and AP CML who are intolerant or have failed (as per ELN 2020 Recommendations) available TKIs known to be active for treatment of their CML. Other key eligibility criteria are Eastern Cooperative Oncology Group performance status 0–2, adequate bone marrow, renal and liver function, and resolved adverse effects of prior therapy. Prior marrow transplant is allowed. CML with point mutations E255, Y253, G250, F317 or Q252 are excluded.
Successive cohorts will receive escalating doses of ELVN-001 starting at 10 mg QD. Dosing will be continuous in 28-day cycles until treatment failure, disease progression or unacceptable toxicity.
A standard 3+3 dose escalation will be used, with PK/pharmacodynamic modeling to identify the RDEs, assuming toxicity is not dose limiting. Safety and efficacy of ELVN-001 will be further explored in CP-CML without T315I mutations and a cohort of T315I mutated CP-CML. Mutational analyses by Sanger and NGS will be conducted at baseline and end of treatment.
Main Outcomes: Primary endpoints are dose limiting toxicities, adverse events, laboratory and ECG abnormalities. Secondary endpoints are PK parameters, response based on BCR-ABL transcript levels by quantitative PCR and hematology.
Conclusions: This FIH study will evaluate dosing, safety, tolerability, PK profile and preliminary efficacy of ELVN-001 in CP-CML with and without T315I mutation.
Study sponsor: Enliven Therapeutics. NCT05304377
Disclosures: Hughes: BMS: Consultancy, Research Funding; Enliven: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Mauro: Sun Pharma/SPARC: Research Funding; AbbVie, Bristol Myers Squibb, Novartis, Pfizer, Takeda: Consultancy, Honoraria, Other: Travel, accommodation, expenses , Research Funding. Branford: Qiagen: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Deng: Enliven Therapeutics: Current Employment, Current holder of stock options in a privately-held company. Wang: Enliven Therapeutics: Current Employment, Current holder of stock options in a privately-held company. Collins: Enliven Therapeutics: Current Employment, Current holder of stock options in a privately-held company. Hochhaus: Novartis: Research Funding; Incyte: Research Funding; BMS: Research Funding; Pfizer: Research Funding.
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