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

Study Overview
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Brief Summary
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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.

Detailed Description
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This first-in-human trial with ELVN-001 is a dose escalation study whose primary purpose is to identify the recommended dose for expansion RDE of single agent ELVN-001 in chronic phase or accelerated phase CML with and 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 RDE safety profile, PK and preliminary evidence of anti-CML activity will be used to inform future development 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 tolerable or benefit from available TKIs.

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

Conditions
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Chronic Myeloid Leukemia

Intervention / Treatment
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* Drug: ELVN-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CML that has failed or the patient is intolerant to available therapies known to be active for treatment of their CML. ECOG performance status of 0 to 2. Adequate hematologic, hepatic and renal function. Exclusion Criteria: Treatment with anti-cancer or anti-CML therapy within 7 days or 5 half-lives, whichever is longer. QTc >470 ms.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: phase 1b expansion arm at recommended dose level 1<br>ELVN-001 administered orally once daily at RDE-1 in CML without T315I mutations | Drug: ELVN-001<br>* orally once daily<br>|
| Experimental: Phase 1b expansion arm at recommended dose level 2<br>ELVN-001 administered orally once daily at RDE-2 in CML without T315I mutations | Drug: ELVN-001<br>* orally once daily<br>|
| Experimental: Phase 1b expansion arm in T315I mutated CML<br>ELVN-001 administered orally once daily at RDE-3 | Drug: ELVN-001<br>* orally once daily<br>|
| Experimental: Phase 1a dose escalation in CML<br>ELVN-001 administered orally once daily in 3+3 dose escalation | Drug: ELVN-001<br>* orally once daily<br>|

What is the study measuring?
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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 adverse events | Adverse events will be used to support that the dose(s) evaluated in expansion is tolerable | up to 3 years | 
| 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 | 

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 | 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: frequency of complete cytogenetic remission (CCyR) | The proportion of patients who achieve CCyR by serum BCR-ABL1 transcript level who are not in CHR at baseline | up to 3 years | 
| Phase 1b: Rate of complete hematologic response (CHR) | The proportion of patients who achieve a CHR who are not in CHR at baseline | up to 3 years |