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

Enliven Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Chronic Myeloid Leukemia

Treatments: Drug: ELVN-001

Study type: Interventional

Funder types: Industry

Identifiers

NCT05304377

ELVN-001-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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180 participants in 4 patient groups

Phase 1a Dose Escalation

Experimental group

Description:

ELVN-001 administered in 3+3 dose escalation

Treatment:

Drug: ELVN-001

Phase 1b Dose Expansion at recommended dose level 1

Experimental group

Description:

ELVN-001 administered at the recommended dose in CML without T315I mutations

Treatment:

Drug: ELVN-001

Phase 1b Dose Expansion at recommended dose level 2

Experimental group

Description:

ELVN-001 administered at a different recommended dose in CML without T315I mutations

Treatment:

Drug: ELVN-001

Phase 1b expansion arm in T315I mutated CML

Experimental group

Description:

ELVN-001 administered at the recommended dose for CML with T315I mutation

Treatment:

Drug: ELVN-001