ELVN-001 for Chronic Myelogenous Leukemia

(CML Trial)

Recruiting at 47 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Enliven Therapeutics

Must not be taking: Anti-cancer, Anti-CML

Disqualifiers: Pancreatitis, QTc >470 ms, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ELVN-001 for individuals with chronic myelogenous leukemia (CML), a type of blood cancer. The main goal is to assess the treatment's safety and determine the optimal dose. Researchers will test ELVN-001 in different groups: those with and without the T315I gene mutation. Suitable candidates for this trial are individuals whose CML has not responded well to other treatments or who cannot tolerate them. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer or anti-CML medications at least 7 days before starting the study drug, or longer if the medication stays in your body for a while (5 half-lives).

Is there any evidence suggesting that ELVN-001 is likely to be safe for humans?

Research shows that ELVN-001 has promising safety results. The data suggest that ELVN-001 is generally well-tolerated compared to other treatments for chronic myeloid leukemia, meaning people usually handle it without severe side effects.

These studies have not reported any serious unwanted effects from the drug. Although testing is still in the early stages, this is a positive sign for its safety in humans. As a Phase 1 study, the main goal is to find a safe dose, so the researchers are still gathering safety information. Participants in earlier trials handled ELVN-001 well, which reassures its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ELVN-001 for chronic myelogenous leukemia (CML) because it offers a new approach compared to traditional treatments like tyrosine kinase inhibitors (TKIs) such as imatinib. Most TKIs struggle with CML cases that involve the T315I mutation, a common resistance issue. ELVN-001 is designed to target this mutation specifically, potentially overcoming resistance that limits the effectiveness of current therapies. Additionally, ELVN-001 aims to provide a focused treatment option for both T315I and non-T315I CML, offering flexibility and hope for a broader range of patients.

What evidence suggests that ELVN-001 might be an effective treatment for chronic myeloid leukemia?

Research has shown that ELVN-001 could be a promising treatment for chronic myelogenous leukemia (CML). In earlier studies, 47% of patients experienced a major reduction in cancer activity within 24 weeks. This finding is significant because it suggests the treatment can effectively target cancer cells. ELVN-001 works by blocking a specific protein essential for the cancer's growth. The treatment also appears safe, with patients tolerating it well. These findings offer hope that ELVN-001 could be a strong option for people with CML, especially if other treatments have not worked. Participants in this trial will receive ELVN-001 in different phases, including dose escalation and expansion phases, to further evaluate its effectiveness and safety. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with chronic myeloid leukemia who have not responded well to, or cannot tolerate, current treatments. Participants should be relatively active (ECOG status 0-2) and have good blood, liver, and kidney function. Those with a recent history of cancer treatment or abnormal heart rhythm (QTc >470 ms) are excluded.

Inclusion Criteria

I can care for myself and am up and about more than 50% of my waking hours.

I have CML and cannot tolerate or haven't responded to current treatments.

My blood, liver, and kidney functions are all within normal ranges.

Exclusion Criteria

I haven't taken any cancer or CML medication in the last 7 days or 5 half-lives, whichever is longer.

QTc >470 ms

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ELVN-001 administered in 3+3 dose escalation to determine the recommended dose for expansion

4 weeks

Dose Expansion

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

up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• ELVN-001

Trial Overview The study is testing ELVN-001's safety and the right dose for people with chronic myeloid leukemia, including those with T315I mutations who haven't had success with tyrosine kinase inhibitors (TKIs).

How Is the Trial Designed?

Group I: Phase 1b expansion (T315I) Experimental Treatment 1 Intervention

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

Group II: Phase 1b Dose Expansion (non-T315I) Experimental Treatment 1 Intervention

ELVN-001 administered at one or more recommended dose(s) for expansion in CML without T315I mutations

Group III: Phase 1a Dose Escalation Experimental Treatment 1 Intervention

ELVN-001 administered in 3+3 dose escalation

Who Is Running the Clinical Trial?

Enliven Therapeutics

Lead Sponsor

Trials

4

Recruited

670+

Published Research Related to This Trial

In a study of 162 newly diagnosed chronic myeloid leukemia patients, combining escalated doses of imatinib with intravenous cytarabine resulted in high rates of treatment response, with 53% achieving a complete molecular response after 5 years.

The study found that higher doses of both imatinib and cytarabine were linked to better treatment outcomes, and the overall survival rate was an impressive 96%, indicating the effectiveness of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia. Deenik, W., Janssen, JJ., van der Holt, B., et al.[2022]

The survival rates for early-phase chronic myelogenous leukemia (CML) have significantly improved due to the use of tyrosine kinase inhibitors (TKIs) like imatinib, nilotinib, and dasatinib.

Monitoring treatment response through complete cytogenetic response and mutational analysis is crucial for managing imatinib resistance, with new agents like ponatinib and bosutinib now available for resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring response to tyrosine kinase inhibitor therapy, mutational analysis, and new treatment options in chronic myelogenous leukemia. Radich, JP.[2019]

Imatinib, a targeted inhibitor of the BCR-ABL fusion protein, has significantly improved survival rates for patients with chronic myelogenous leukemia (CML), but some patients develop resistance or intolerance to this therapy.

Second-generation tyrosine kinase inhibitors like nilotinib and dasatinib, along with newer options like ponatinib and bosutinib, provide additional treatment choices for CML, enhancing patient outcomes and quality of life, and ongoing clinical trials are exploring the best ways to use these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy in chronic myelogenous leukemia: where do emerging therapies fit within current treatment regimens? Mauro, MJ., Talpaz, M., Radich, JP.[2017]

The updated European LeukemiaNet (ELN) recommendations emphasize the importance of regular monitoring for chronic myeloid leukemia (CML) patients, requiring cytogenetic assessments at 3, 6, 12, and 18 months, and molecular monitoring every 3 months to evaluate treatment response.

Imatinib at a dose of 400 mg daily remains the first-line treatment for CML, with options for second-generation tyrosine kinase inhibitors for patients who show suboptimal response or treatment failure, highlighting a structured approach to managing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. Baccarani, M., Cortes, J., Pane, F., et al.[2023]

Recent advances in the treatment of chronic myeloid leukemia (CML) and BCR-ABL1-negative myeloproliferative neoplasms (MPNs) include updates on JAK2 inhibitors and the use of alpha interferons, which show promise in targeting these conditions.

The review highlights the importance of monitoring strategies and the potential for targeting CML stem cells and their niche, which could lead to more effective therapies and improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary insights into the pathogenesis and treatment of chronic myeloproliferative neoplasms. Mughal, TI., Abdel-Wahab, O., Rampal, R., et al.[2019]

Citations

1. ir.enliventherapeutics.com ir.enliventherapeutics.com/news-releases/news-release-details/enliven-therapeutics-announces-updated-positive-data-phase-1-0

Enliven Therapeutics Announces Updated Positive Data ... Reported cumulative MMR rate of 47% (25 of 53) by 24 weeks with 32% (13 of 41) of patients achieving. MMR by 24 weeks, which continues to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05304377

NCT05304377 | A Phase 1a/1b Study of ELVN-001 for the ... 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 ...

3. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/5515/757402/Abstract-5515-ELVN-001-a-highly-selective-ATP

ELVN-001, a highly selective ATP-competitive ABL1 tyrosine ... ELVN-001 is a potent, highly selective ABL1 Tyrosine Kinase Inhibitor (TKI) currently being evaluated in a Phase 1a/b clinical trial in patients with BCR-ABL1- ...

4. onclive.com onclive.com/view/elvn-001-appears-safe-and-effective-in-relapsed-refractory-cml

ELVN-001 Appears Safe and Effective in Relapsed ... We continue to see categorical improvements in molecular response, and the drug remains well tolerated with an encouraging safety profile.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025019408

CML-575: ENABLE: A Phase 1a/1b Study of ELVN-001, a ... ELVN-001 is a highly selective active site tyrosine kinase inhibitor (TKI) of BCR::ABL1 with broad pre-clinical activity against native and mutant BCR::ABL1.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05304377

NCT05304377 | A Phase 1a/1b Study of ELVN-001 for the ... 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06787144

NCT06787144 | ELVN-001 for the Treatment of Chronic ... The purpose of this study is to evaluate the safety, tolerability and determine the recommended dose for further clinical evaluation of ELVN-001 in Japanese ...

8. enliventherapeutics.com enliventherapeutics.com/file.cfm/39/docs/esh-icml_2024_elvn-001_28_sept_2024-final.pdf

Preliminary safety and efficacy of ELVN-001, a selective ... previously discontinued asciminib and ponatinib due to lack of efficacy. Data cutoff date: 25 June 2024. BCR::ABL1 = breakpoint cluster region- ...