LY3214996 for Acute Myeloid Leukemia

Overseen By Rahul Vedula, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must be taking: Antifungal agents

Must not be taking: Tyrosine kinase inhibitors

Disqualifiers: Chemotherapy, Major surgery, CNS leukemia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days

17 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is evaluating a targeted therapy as a possible treatment for acute myeloid leukemia (AML) that has returned or not responded to standard treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop all current medications, but it does mention that you cannot take certain antifungal medications if they are moderate or strong CYP3A4 inhibitors, unless specified in the trial arm. Additionally, you should not have had chemotherapy, investigational therapy, immunotherapy, or radiotherapy within 2 weeks before starting the trial.

What makes the drug LY3214996 (Temuterkib) unique for treating acute myeloid leukemia?

LY3214996 (Temuterkib) is a novel treatment being investigated for acute myeloid leukemia (AML), which is a challenging condition with limited effective options. Unlike traditional chemotherapy, this drug is part of a new wave of targeted therapies that aim to specifically attack cancer cells based on their unique characteristics, potentially offering a more precise and less toxic treatment approach. ^{1 2 3 4 5}

Research Team

Rahul Vedula, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with acute myeloid leukemia (AML) that has returned or is unresponsive to standard treatments can join this trial. They must be able to sign consent, not have had a stem cell transplant recently, and agree to use contraception. Those on certain antifungal drugs affecting liver enzyme activity are included in specific arms of the study.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document.

I can take care of myself but might not be able to do heavy physical work.

I can swallow and keep down pills.

Exclusion Criteria

I have not had major surgery in the last 4 weeks.

I do not have any severe illnesses that could interfere with the study.

I am not pregnant, not breastfeeding, and if capable of becoming pregnant, I have a negative pregnancy test.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY3214996 by mouth once daily continuously throughout each treatment cycle

21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• LY3214996

Trial Overview The trial is testing LY3214996, a targeted therapy for AML patients who haven't responded well to other treatments. It's designed to see if this drug can help where others haven't by blocking cancer growth signals.

Participant Groups

Group I: Arm B: Dose Escalation LY3214996 Experimental Treatment 1 Intervention

-LY3214996 will be administered by mouth once daily continuously throughout each treatment cycle for patients with inhibitors for fungal prophylaxis/treatment

Group II: Arm A: Dose Expansion LY3214996 Experimental Treatment 1 Intervention

-LY3214996 will be administered by mouth once daily continuously throughout each treatment cycle for patients without inhibitors for fungal prophylaxis/treatment

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

AMG 232, an investigational drug for relapsed/refractory acute myeloid leukemia (AML), was found to have acceptable safety and pharmacokinetics, with no dose-limiting toxicities at doses up to 360 mg when used alone, although gastrointestinal side effects were noted at higher doses.

In terms of efficacy, 1 out of 30 evaluable patients achieved complete remission, and 31% of patients with wild-type TP53 responded to treatment, indicating potential effectiveness, especially in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia. Erba, HP., Becker, PS., Shami, PJ., et al.[2023]

A comprehensive review of 397 phase II trials and 28 phase III trials from 2000 to 2020 revealed that targeted therapies for acute myeloid leukemia (AML) have limited success, with only eight drugs receiving FDA approval, and three of those not demonstrating overall survival benefits.

Repurposed drugs were less likely to progress in clinical trials compared to those specifically designed for AML, highlighting the need for future research to focus on both targeted and non-targeted therapies, as well as endpoints that assess patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two decades of targeted therapies in acute myeloid leukemia. Cucchi, DGJ., Polak, TB., Ossenkoppele, GJ., et al.[2021]

The study evaluated MK-8242 in 26 subjects with refractory/recurrent acute myeloid leukemia (AML), finding that a 7on/14off dosing regimen (210mg or 300mg BID) had a more favorable safety profile compared to the 7on/7off regimen, with no dose-limiting toxicities observed in the higher doses.

Efficacy was demonstrated with responses including one partial response and one complete response in patients, suggesting that MK-8242, an HDM2 inhibitor, warrants further investigation for treating AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML). Ravandi, F., Gojo, I., Patnaik, MM., et al.[2018]

Recent advancements in genomics and molecular biology have significantly enhanced our understanding of acute myeloid leukemia (AML), a disease known for its clinical and genetic diversity and poor prognosis.

Since 2017, there have been new drug approvals for AML, particularly focusing on epigenetic-targeted therapies that are currently in pre-clinical and clinical development, marking a significant shift in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the understanding and treatment of acute myeloid leukemia. Watts, J., Nimer, S.[2023]

Recent advancements in targeted therapies for acute myeloid leukemia (AML) include novel agents like pinometostat, KO-539, SYNDX-5613, and APR-246, which specifically target mutations associated with AML, showing promise in early-phase clinical trials.

In addition to mutation-specific therapies, new drug classes such as BET inhibitors, polo-like kinase inhibitors, and MDM2 inhibitors are being explored, offering potential treatments for AML cases without targetable mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Targeted Therapeutics in Acute Myeloid Leukemia: an Embarrassment of Riches. Grieselhuber, NR., Mims, AS.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Two decades of targeted therapies in acute myeloid leukemia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A phase I trial of the human double minute 2 inhibitor (MK-8242) in patients with refractory/recurrent acute myelogenous leukemia (AML). [2018]

4. England pubmed.ncbi.nlm.nih.gov

Recent advances in the understanding and treatment of acute myeloid leukemia. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Novel Targeted Therapeutics in Acute Myeloid Leukemia: an Embarrassment of Riches. [2023]