LY3410738 for Blood Cancers

Not currently recruiting at 50 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must not be taking: Venetoclax, PPIs, Strong CYP3A4 drugs

Disqualifiers: Concurrent malignancy, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called LY3410738 for certain blood cancers with specific genetic changes (IDH1 and/or IDH2 mutations). Researchers aim to assess the effectiveness of this treatment both alone and in combination with other drugs. Individuals may qualify if they have been diagnosed with a type of blood cancer, such as acute myeloid leukemia (AML), that has returned or is not responding to standard treatments, and they possess one of these genetic mutations. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial requires stopping certain medications, like strong CYP3A4 inhibitors or inducers, P-gp inhibitors, and proton pump inhibitors, before starting the study drug. However, some antifungal inhibitors of CYP3A4 are allowed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LY3410738 is generally safe based on earlier studies. Patients typically handled the treatment well, and no major safety issues emerged. Some side effects occurred, but they were mostly manageable. LY3410738 also successfully blocked a harmful substance related to certain cancer mutations. This suggests the treatment could be a promising option for individuals with specific genetic markers in their blood cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about LY3410738 because it represents a fresh approach to treating blood cancers, particularly those with IDH1 and IDH2 mutations. Unlike current standard treatments, which often focus on general chemotherapy or targeted therapies for specific mutations, LY3410738 directly inhibits mutant forms of the IDH1 enzyme, potentially correcting the abnormal cell growth driving these cancers. This specificity means it could offer a more targeted attack against cancer cells, potentially with fewer side effects. Additionally, when combined with drugs like Venetoclax and Azacitidine, LY3410738 might enhance therapeutic effects, offering hope for patients who have not responded to other treatments.

What evidence suggests that this trial's treatments could be effective for blood cancers?

Research has shown that LY3410738 may help treat certain blood cancers with specific genetic changes. It targets changes in the IDH1 and IDH2 genes, often found in advanced blood cancers like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In this trial, participants will join different treatment arms, including monotherapy and combination therapy with LY3410738, to evaluate its effectiveness. Studies have demonstrated that LY3410738 is effective for patients with these genetic changes, especially those whose AML has returned or not responded to other treatments. This drug blocks a protein that aids cancer cell growth. Early results suggest that LY3410738 can slow or stop the growth of these cancers. ^{1 6 7 8 9}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with advanced blood cancers (like AML) that have specific IDH1 or IDH2 mutations. Participants must be able to take oral medication, follow birth control measures if of reproductive potential, and have an ECOG score of 0-2 indicating they are relatively active. They can't join if they've had certain recent treatments, other active cancers, major surgery, uncontrolled infections, significant heart issues, or been on strong CYP3A4 inhibitors.

Inclusion Criteria

-- For Dose Escalation Arm C and Dose Expansion Cohort 5:

Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation

My cancer has a specific IDH1 or IDH2 mutation.

Exclusion Criteria

I have never been treated with venetoclax.

Any serious underlying medical or psychiatric condition (e.g. alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the patient to understand informed consent or that in the opinion of the Investigator would contraindicate the patient's participation in the study or confound the results of the study

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of LY3410738 to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

Up to 30 months

Dose Expansion

Participants are enrolled into 5 cohorts to further evaluate safety and clinical activity of LY3410738

Up to 30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3410738

Trial Overview The study tests LY3410738—an oral drug targeting mutated enzymes in blood cancer cells—alone or with standard therapies like Venetoclax and Azacitidine. It's a Phase 1 trial where everyone gets the experimental treatment but at different doses to find the safest and most effective amount.

How Is the Trial Designed?

Group I: Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine) Experimental Treatment 3 Interventions

Patients with no prior venetoclax therapy and not requiring a strong CYP3A4 inhibitor for active treatment within 7 days of starting LY3410738.

Group II: Dose Escalation Arm B (Monotherapy) Experimental Treatment 1 Intervention

Patients requiring a strong CYP3A4 inhibitor for active management or prevention of a lifethreatening condition, such as an azole administered to prevent invasive fungal infection.

Group III: Dose Escalation Arm A (Monotherapy) Experimental Treatment 1 Intervention

Patients not requiring a strong cytochrome P450 3A4 (CYP3A4) inhibitor.

Group IV: Cohort 5 Experimental Treatment 3 Interventions

Patients with newly diagnosed AML, R/R AML, or other advanced hematologic malignancy harboring IDH1 and/or IDH2 mutations with no prior venetoclax therapy. Strong CYP3A4 inhibitor allowed but not required.

Group V: Cohort 4 Experimental Treatment 1 Intervention

Patients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations.

Group VI: Cohort 3 Experimental Treatment 1 Intervention

Patients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation.

Group VII: Cohort 2 Experimental Treatment 1 Intervention

Patients with R/R AML harboring an IDH1 R132 mutation who have not received a prior IDH inhibitor.

Group VIII: Cohort 1 Experimental Treatment 1 Intervention

Patients with relapsed/refractory (R/R) AML harboring an IDH1 R132 mutation who have received a prior IDH inhibitor.

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead 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

Loxo Oncology, Inc.

Industry Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04603001

NCT04603001 | Study of Oral LY3410738 in Patients With ... Patients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations. Intervention/Treatment, Drug : LY3410738. Oral LY3410738.

2. ctv.veeva.com ctv.veeva.com/study/study-of-oral-ly3410738-in-patients-with-advanced-hematologic-malignancies-with-idh1-or-idh2-mutatio

Study of Oral LY3410738 in Patients With Advanced ... Patients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation.

3. synapse.patsnap.com synapse.patsnap.com/blog/decoding-ly-3410738-a-comprehensive-study-of-its-randd-trends-and-its-clinical-results-in-2023-aacr

Decoding LY-3410738: a comprehensive study of its R&D ... Specifically, LY-3410738 has demonstrated efficacy in the treatment of acute myeloid leukemia ... In pts with IDH1m cancers, LY3410738 achieved ...

4. researchgate.net researchgate.net/publication/346691266_A_Phase_1_Study_of_LY3410738_a_First-in-Class_Covalent_Inhibitor_of_Mutant_IDH_in_Advanced_Myeloid_Malignancies_Trial_in_Progress

A Phase 1 Study of LY3410738, a First-in-Class Covalent ... Once the RP2D is determined, patients will be enrolled into one of 4 dose expansion cohorts based on IDH mutation, myeloid malignancy, and prior therapy, ...

5. delta.larvol.com delta.larvol.com/Products/?ProductId=60bf0fed-873d-43ac-8b89-e196c7ca3c63

LY3410738 / Eli Lilly - Cholangiocarcinoma Journal • Acute Myelogenous Leukemia • Biliary Cancer • Brain Cancer • Cholangiocarcinoma • Glioma • Hematological Malignancies • Leukemia • Metabolic Disorders ...

6. trials.lilly.com trials.lilly.com/en-US/trial/257016

Study of Oral LY3410738 in Patients With ... - Lilly Trials The main purpose of this study is to learn more about the safety, side effects, and early effectiveness of LY3410738. LY3410738 may be used to treat blood ...

7. withpower.com withpower.com/trial/phase-1-preleukemia-11-2020-71396

LY3410738 for Blood Cancers · Info for Participants This trial is for adults with advanced blood cancers (like AML) that have specific IDH1 or IDH2 mutations. Participants must be able to take oral medication, ...

8. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT098/725320/Abstract-CT098-A-first-in-human-phase-1-study-of

Abstract CT098: A first-in-human phase 1 study of LY3410738 ... Conclusions: LY3410738 demonstrated a favorable safety profile with potent and sustained D-2-HG inhibition in pts with IDH1/2m advanced solid ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11546319/

Efficacy and safety of IDH inhibitors in IDH-mutated cancers The overall efficacy of IDH inhibitors in treating cancers with IDH mutations is superior to that of conventional medical therapy, potentially providing more ...