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

NCT ID: NCT04603001

Last Updated: 2025-06-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

260 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-19

Study Completion Date

2026-05-31

Brief Summary

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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

Detailed Description

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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

Conditions

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Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS) Chronic Myelomonocytic Leukemia (CMML) Myeloproliferative Neoplasms (MPNs)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation Arm A (Monotherapy)

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

Group Type EXPERIMENTAL

LY3410738

Intervention Type DRUG

Oral LY3410738

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.

Group Type EXPERIMENTAL

LY3410738

Intervention Type DRUG

Oral LY3410738

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.

Group Type EXPERIMENTAL

LY3410738

Intervention Type DRUG

Oral LY3410738

Venetoclax

Intervention Type DRUG

Oral venetoclax

Azacitidine

Intervention Type DRUG

Subcutaneous or intravenous azacitidine

Cohort 1

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

Group Type EXPERIMENTAL

LY3410738

Intervention Type DRUG

Oral LY3410738

Cohort 2

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

Group Type EXPERIMENTAL

LY3410738

Intervention Type DRUG

Oral LY3410738

Cohort 3

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

Group Type EXPERIMENTAL

LY3410738

Intervention Type DRUG

Oral LY3410738

Cohort 4

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

Group Type EXPERIMENTAL

LY3410738

Intervention Type DRUG

Oral LY3410738

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.

Group Type EXPERIMENTAL

LY3410738

Intervention Type DRUG

Oral LY3410738

Venetoclax

Intervention Type DRUG

Oral venetoclax

Azacitidine

Intervention Type DRUG

Subcutaneous or intravenous azacitidine

Interventions

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LY3410738

Oral LY3410738

Intervention Type DRUG

Venetoclax

Oral venetoclax

Intervention Type DRUG

Azacitidine

Subcutaneous or intravenous azacitidine

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status

UCLA Medical Center

Los Angeles, California, United States

Site Status

University of California, Davis - Health Systems

Sacramento, California, United States

Site Status

H Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Hospital

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Linear Clinical Research

Nedlands, Western Australia, Australia

Site Status

Cliniques universitaires Saint-Luc

Brussels, , Belgium

Site Status

BC Cancer Vancouver

Vancouver, British Columbia, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)

Helsinki, , Finland

Site Status

Institut Paoli-Calmettes

Marseille, , France

Site Status

Hopital Saint Louis

Paris, , France

Site Status

Centre hospitalier universitaire de Haut Leveque

Pessac, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Institut Claudius Regaud

Toulouse, , France

Site Status

Medizinische Hochschule Hanover

Hanover, Lower Saxony, Germany

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

National University Cancer Institute

Singapore, , Singapore

Site Status

Singapore General Hospital

Singapore, , Singapore

Site Status

Asan Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], South Korea

Site Status

Samsung Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Clinico Y Provincial Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status

Hospital Universitario La Fe de Valencia

Valencia, , Spain

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Countries

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United States Australia Belgium Canada Finland France Germany Israel Singapore South Korea Spain Taiwan

Related Links

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https://trials.lillytrialguide.com/en-US/trial/5zLVhd8jkDNg8KcTGH3Tf9?nickname=I9Y-OX-JDHB

Study of LY3410738 in Patients with Advanced Blood Cancers with a Change in the IDH1 or IDH2 Gene

Other Identifiers

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2020-002830-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

I9Y-OX-JDHB

Identifier Type: OTHER

Identifier Source: secondary_id

LOXO-IDH-20001

Identifier Type: OTHER

Identifier Source: secondary_id

18076

Identifier Type: -

Identifier Source: org_study_id

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