Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations

July 21, 2026 updated by: Eli Lilly and Company

A Phase 1 Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations

This is an open-label, multi-center Phase 1 study of LY3410738, an oral, covalent isocitrate dehydrogenase (IDH) inhibitor, in patients with IDH1 and/or IDH2-mutant advanced hematologic malignancies who may have received standard therapy

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study includes 2 parts: dose escalation and dose expansion. The dose escalation will enroll eligible patients with select IDH-mutant advanced hematologic malignancies. Once the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of LY3410738 is established, the dose expansion will begin and enroll into 5 cohorts to further evaluate safety and clinical activity

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
260

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • The Alfred Hospital
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Linear Clinical Research
  • Belgium
      • Brussels, Belgium, 1200
        • Cliniques universitaires Saint-Luc
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer Vancouver
    • Ontario
      • Toronto, Ontario, Canada, M5G2M9
        • Princess Margaret Hospital
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
  • Finland
      • Helsinki, Finland, 00290
        • Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
  • France
      • Marseille, France, 13273
        • Institut Paoli-Calmettes
      • Paris, France, 75010
        • Hopital Saint Louis
      • Pessac, France, 33604
        • Centre hospitalier universitaire de Haut Leveque
      • Pierre-Bénite, France, 69495
        • Centre Hospitalier LYON SUD
      • Toulouse, France, 31059
        • Institut Claudius Regaud
  • Germany
    • Lower Saxony
      • Hanover, Lower Saxony, Germany, 30625
        • Medizinische Hochschule Hanover
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Medical Center
  • Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital
      • Singapore, Singapore, 119228
        • National University Cancer Institute
  • South Korea
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
    • Seoul-teukbyeolsi [Seoul]
      • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 06351
        • Samsung Medical Center
      • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 05505
        • Asan Medical Center
  • Spain
      • Barcelona, Spain, 8036
        • Clinico Y Provincial Barcelona
      • Madrid, Spain, 28040
        • Hospital Universitario Fundación Jiménez Díaz
      • Valencia, Spain, 46026
        • Hospital Universitario La Fe de Valencia
  • Taiwan
      • Taichung, Taiwan, 40447
        • China Medical University Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Sacramento, California, United States, 95817
        • University of California, Davis - Health Systems
    • Florida
      • Tampa, Florida, United States, 33612-9497
        • H Lee Moffitt Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • New York
      • Buffalo, New York, United States, 14263-0002
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina at Chapel Hill
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Advanced IDH mutant hematologic malignancy including:

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

    • Patients with newly diagnosed AML who are 75 years or older or have comorbidities that preclude the use of intensive chemotherapy
    • Patients with R/R AML (US only)
  • Patients must have received prior therapy
  • Blasts at least 5% in bone marrow.
  • Patients must have a qualifying IDH1 R132, IDH2 R140 or IDH2 R172 mutation
  • Eastern Cooperative Oncology Group (ECOG) 0 to 2
  • Adequate organ function
  • Ability to swallow capsules or tablets
  • Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
  • Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment.

Exclusion Criteria:

  • Investigational agent or anticancer therapy within 2 weeks or 5 half-lives, whichever is shorter; or investigational monoclonal antibody within 4 weeks prior to planned start of LY3410738

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

    • Prior venetoclax treatment is not allowed.
    • Patients are allowed to receive up to 1 cycle of single agent azacitidine or azacitidine plus venetoclax while waiting for results of locally obtained molecular profiling, including IDH1/IDH2 mutational status, prior to starting on study.
  • Major surgery within 4 weeks prior to planned start of LY3410738.
  • Active, uncontrolled clinically significant systemic bacterial, viral, fungal or parasitic infection or an unexplained fever > 38.5ºC during Screening or on the first day of study drug administration.
  • Another concurrent malignancy requiring active therapy.
  • Active central nervous system involvement
  • Any unresolved toxicities from prior therapy greater than CTCAE v5.0 Grade 2 at the time of starting study treatment except for alopecia.
  • History of hematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy within 60 days of the first dose of LY3410738.
  • Clinically significant cardiovascular disease
  • Active hepatitis B virus (HBV)
  • Active hepatitis C virus (HCV)
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or P- glycoprotein (P-gp) inhibitor, with the exception of patients being treated with allowed antifungal inhibitors of CYP3A4
  • Treatment with proton pump inhibitor (PPIs) within 7 days of starting LY3410738
  • 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
  • Known human immunodeficiency virus (HIV), excluded due to potential drug-drug interactions between antiretroviral medications and LY3410738
  • Pregnancy, lactation or plan to breastfeeding during the study or within 90 days of the last dose of study intervention
  • Known hypersensitivity to any of the components of LY3410738 or its formulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose Escalation Arm A (Monotherapy)
Patients not requiring a strong cytochrome P450 3A4 (CYP3A4) inhibitor.
Drug: LY3410738
Oral LY3410738
Experimental: Dose Escalation Arm B (Monotherapy)
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.
Drug: LY3410738
Oral LY3410738
Experimental: Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine)
Patients with no prior venetoclax therapy and not requiring a strong CYP3A4 inhibitor for active treatment within 7 days of starting LY3410738.
Drug: LY3410738
Oral LY3410738
Drug: Venetoclax
Oral venetoclax
Drug: Azacitidine
Subcutaneous or intravenous azacitidine
Experimental: Cohort 1
Patients with relapsed/refractory (R/R) AML harboring an IDH1 R132 mutation who have received a prior IDH inhibitor.
Drug: LY3410738
Oral LY3410738
Experimental: Cohort 2
Patients with R/R AML harboring an IDH1 R132 mutation who have not received a prior IDH inhibitor.
Drug: LY3410738
Oral LY3410738
Experimental: Cohort 3
Patients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation.
Drug: LY3410738
Oral LY3410738
Experimental: Cohort 4
Patients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations.
Drug: LY3410738
Oral LY3410738
Experimental: Cohort 5
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.
Drug: LY3410738
Oral LY3410738
Drug: Venetoclax
Oral venetoclax
Drug: Azacitidine
Subcutaneous or intravenous azacitidine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
Time Frame: Up to 30 months
For Dose Escalation
Up to 30 months
To assess the activity of LY3410738 as measured by the overall response rate (ORR) per the Investigator assessment
Time Frame: Up to 30 months
For Dose Expansion
Up to 30 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To determine the safety profile and tolerability of LY3410738 including acute and chronic toxicities by collecting and evaluating adverse events and treatment emergent adverse events
Time Frame: Up to 30 months
For Dose Escalation
Up to 30 months
To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
Time Frame: Up to 30 months
For Dose Escalation
Up to 30 months
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma
Time Frame: Up to 30 months
For Dose Escalation
Up to 30 months
To assess the activity of LY3410738 as measured by the overall response rate (ORR) per Investigator assessment
Time Frame: Up to 30 months
For Dose Escalation
Up to 30 months
To assess the activity of LY3410738 as measured by Best Overall Response (BOR) per Investigator assessment
Time Frame: Up to 30 months
For Dose Expansion
Up to 30 months
To assess the activity of LY3410738 by Complete Remission (CR) Rate (CRR) plus partial hematologic recovery (AML patients)
Time Frame: Up to 30 months
For Dose Expansion
Up to 30 months
To assess the activity of LY3410738 by Duration of Response
Time Frame: Up to 30 months
For Dose Expansion
Up to 30 months
To assess the activity of LY3410738 by Hematologic improvement in patients with MDS
Time Frame: Up to 30 months
For Dose Expansion
Up to 30 months
To determine the safety profile and tolerability of LY3410738 including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events
Time Frame: Up to 30 months
For Dose Expansion
Up to 30 months
To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
Time Frame: Up to 30 months
For Dose Expansion
Up to 30 months
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma.
Time Frame: Up to 30 months
For Dose Expansion
Up to 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Loxo Oncology, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: 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), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 19, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 3, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 12, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 21, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 26, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 18076
  • LOXO-IDH-20001 (Other Identifier: Eli Lilly and Company)
  • 2020-002830-33 (EudraCT Number)
  • I9Y-OX-JDHB (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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