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

NCT04603001 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: 180762020-002830-33I9Y-OX-JDHBLOXO-IDH-20001
• Study Type: interventional
• Target: 260
• Locations: 12 countries
• Sites: 37

Brief Summary

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

Conditions

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

Keywords

Loxo; LY3410738; isocitrate dehydrogenase; IDH; IDH1; IDH2; R132; R140; R172; 2-hydroxyglutarate; 2-HG; Advanced Hematologic Malignancies; Blasts; Acute Myeloid Leukemia; AML; Relapsed/refractory AML; R/R AML; Myelodysplastic Syndrome; MDS; Chronic Myelomonocytic Leukemia; CMML; Myeloproliferative Neoplasms; MPN; Advanced Hematologic Cancers; Ivosidenib; AG-120; Vorasidenib; AG-881; Olutasidenib; FT-2102; BAY1436032; DS-1001; IDH-305; Enasidenib; AG-221; Arginine 132; Arginine 140; Arginine 172

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)

  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

  For Dose Expansion

  Up to 30 months

Secondary Outcomes (11)

• 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

  Up to 30 months

• To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points

  Up to 30 months

• To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma

  Up to 30 months

• To assess the activity of LY3410738 as measured by the overall response rate (ORR) per Investigator assessment

  Up to 30 months

• To assess the activity of LY3410738 as measured by Best Overall Response (BOR) per Investigator assessment

  Up to 30 months

Study Arms (8)

Dose Escalation Arm A (Monotherapy)

EXPERIMENTAL

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

Drug: LY3410738

Dose Escalation Arm B (Monotherapy)

EXPERIMENTAL

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

Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine)

EXPERIMENTAL

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

Drug: LY3410738; Drug: Venetoclax; Drug: Azacitidine

Cohort 1

EXPERIMENTAL

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

Drug: LY3410738

Cohort 2

EXPERIMENTAL

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

Drug: LY3410738

Cohort 3

EXPERIMENTAL

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

Drug: LY3410738

Cohort 4

EXPERIMENTAL

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

Drug: LY3410738

Cohort 5

EXPERIMENTAL

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; Drug: Venetoclax; Drug: Azacitidine

Interventions

LY3410738 DRUG

Oral LY3410738

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Dose Escalation Arm A (Monotherapy); Dose Escalation Arm B (Monotherapy); Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine)

Venetoclax DRUG

Oral venetoclax

Cohort 5; Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine)

Azacitidine DRUG

Subcutaneous or intravenous azacitidine

Cohort 5; Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (37)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of California, Davis - Health Systems

Sacramento, California, 95817, United States

Location

H Lee Moffitt Cancer Center

Tampa, Florida, 33612-9497, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Hospital

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0002, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

BC Cancer Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

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

Helsinki, 00290, Finland

Location

Institut Paoli-Calmettes

Marseille, 13273, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Centre hospitalier universitaire de Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Medizinische Hochschule Hanover

Hanover, Lower Saxony, 30625, Germany

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

National University Cancer Institute

Singapore, 119228, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Asan Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], 05505, South Korea

Location

Samsung Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], 06351, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Clinico Y Provincial Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario La Fe de Valencia

Valencia, 46026, Spain

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 26, 2020
• Study Start: November 19, 2020
• Primary Completion: July 3, 2023
• Study Completion: May 1, 2026
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3); CA (3); FR (5); US (12); BE (1); DE (1); AU (3); IL (1); FI (1); SG (2); ES (3); TW (2)