Study of LY3410738 Administered to Patients With Advanced Solid Tumors With IDH1 or IDH2 Mutations

NCT04521686 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: 180772020-002863-77I9Y-OX-JDHCLOXO-IDH-20002
• Study Type: interventional
• Target: 200
• Locations: 9 countries
• Sites: 33

Brief Summary

This is an open-label, multicenter Phase 1 study to evaluate safety, tolerability and preliminary efficacy of oral LY3410738 in patients with isocitrate dehydrogenase 1 (IDH1) arginine 132 (R132)-mutant advanced solid tumors, including but not limited to cholangiocarcinoma, chondrosarcoma, and glioma or isocitrate dehydrogenase 2 (IDH2) arginine 140 (R140) or arginine 172 (R172) mutant cholangiocarcinoma.

Conditions

Cholangiocarcinoma; Chondrosarcoma; Glioma; Any Solid Tumor

Keywords

IDH1; CNS tumor; Cholangiocarcinoma; Chondrosarcoma; Glioma; Glioblastoma; Solid tumor; Primary CNS tumor; Colon cancer; Cancer of the Colon; Colon Neoplasms; Colonic Cancer; Neoplasms, Colonic; Malignant tumor of Breast; Mammary Cancer; Mammary Carcinoma, Human; Mammary Neoplasm, Human; Neoplasms, Breast; Tumors, Breast; Human Mammary Carcinoma; Malignant Neoplasm of Breast; Breast Carcinoma; Breast Tumors; Cancer of the Breast; Breast Neoplasms; Breast Cancer; Thyroid cancer; Prostate cancer; Melanoma; IDH1 R132

Outcome Measures

Primary Outcomes (1)

• Recommended Phase 2 Dose (RP2D)

  Up to 24 months

Secondary Outcomes (5)

• Objective Response Rate

  Up to 24 months

• Assess the safety and tolerability of LY3410738 when administered alone or in combination with cisplatin plus gemcitabine or in combination with durvalumab

  Up to 24 months

• To assess the preliminary anti-tumor activity of LY3410738 when administered alone or in combination with cisplatin plus gemcitabine or in combination with durvalumab

  Up to 24 months

• Characterize PK properties of LY3410738 when administered alone or in combination with cisplatin plus gemcitabine or in combination with durvalumab

  Up to 24 months

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

  Up to 24 months

Study Arms (2)

LY3410738

EXPERIMENTAL

Phase 1 dose escalation - Multiple doses of LY3410738

Drug: LY3410738

LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumab

EXPERIMENTAL

Phase 1 dose expansion - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of LY3410738 alone or in combination with gemcitabine plus cisplatin or in combination with durvalumab

Drug: LY3410738; Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab

Interventions

LY3410738 DRUG

Oral LY3410738

LY3410738; LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumab

Gemcitabine DRUG

Intravenous gemcitabine

Also known as: LY188011

LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumab

Cisplatin DRUG

Intravenous cisplatin

LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumab

Durvalumab DRUG

Intravenous durvalumab

LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumab

Eligibility Criteria

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

You may qualify if:

• Evidence of IDH1 R132 mutation (any solid tumor) or circulating tumor DNA IDH2 R140 or IDH2 R172 mutation (cholangiocarcinoma only) as determined by molecular testing performed at a CLIA, ISO/IEC, CAP, or other similarly certified laboratory. For cholangiocarcinoma, chondrosarcoma, and glioma, molecular testing can be performed on tumor tissue or circulating tumor DNA. For all other solid tumor types, molecular testing must be performed on tumor tissue.
• Availability of an archived tumor tissue sample. Patients without an available archival tumor tissue sample must be discussed with the sponsor's Medical Monitor prior to enrollment.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• At least 18 years of age.
• 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.
• For cholangiocarcinoma patients, must have adequate biliary drainage (per investigator's discretion), with no evidence of ongoing infection.
• 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. Patients enrolled to Dose Expansion Cohort 4 shall also follow cisplatin/gemcitabine contraception duration requirements as determined by labels and/or local guidelines. Patients enrolled in dose expansion Cohort 5 should follow durvalumab contraception duration requirements as determined by the durvalumab label and/or local guidelines.
• Monotherapy Dose Escalation:
• A locally advanced or metastatic solid tumor, where standard curative or palliative measures are no longer effective or are not considered appropriate or safe in the opinion of the investigator.
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate by tumor type.
• Prior IDH1 inhibitor treatment is permitted.
• Monotherapy Dose Expansion Cohort 1:
• Histologically or cytologically confirmed diagnosis of advanced or metastatic cholangiocarcinoma, following 1 to 2 lines of prior systemic treatment for advanced disease. Prior IDH1 inhibitor treatment is not permitted.

You may not qualify if:

• Had an investigational agent or anticancer therapy within 2 weeks; or investigational monoclonal antibody within 4 weeks prior to planned start of LY3410738.
• Had major surgery within 4 weeks prior to planned start of LY3410738.
• Had radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment, except for patients receiving whole brain radiotherapy, which must be completed at least 4 weeks prior to the first dose of study treatment.
• Patients with cholangiocarcinoma: underwent hepatic radiation, chemoembolization and radiofrequency ablation, radioembolization or other locoregional therapy \<4 weeks, have history of hepatic encephalopathy of any grade, have ascites requiring intervention such as diuretics or paracentesis, have ongoing cholangitis, have mixed hepatocellular biliary tract cancer histology or history of liver transplant.
• Have active CNS metastases are not eligible. Patients with asymptomatic and treated brain metastases may participate provided that they are stable and are not requiring steroid treatment. Patients with suspected or confirmed leptomeningeal disease are not eligible even if treated.
• Have primary CNS tumors are eligible provided that they do not have leptomeningeal disease and are on a stable or decreasing steroid dose for 7 days prior to screening. Patients with evidence of intracranial hemorrhage either by MRI or CT are not eligible
• Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 at the time of starting study treatment except for alopecia.
• Have clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of study treatment.
• Have active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and the sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
• Known active hepatitis B virus (HBV). Note: Controlled (treated) hepatitis will be allowed if they meet the following criteria, antiviral therapy for HBV must be given for at least 1 month prior to first dose of study drug, and HBV viral load must be less than 2000 IU/ml (104 copies/ml) prior to the first dose of study drug. Those on active HBV therapy with viral loads under 2000 IU/ml (104 copies/ml) should stay on the same therapy throughout the study treatment (Appendix E).
• Known active hepatitis C virus (HCV). Note: Untreated patients with chronic infection by HCV are allowed on study. In addition, successfully treated patients with chronic infection by HCV (defined as sustained virologic response SVR12 or SVR24) are allowed, as long as a minimum of 4 weeks has elapsed between achieving sustained viral response (SVR12 or SVR24) and starting study drug.
• Known human immunodeficiency virus (HIV); excluded due to potential drug-drug interactions between anti-retroviral medications and LY3410738.
• Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (Appendix F) and/or P-gp inhibitors (Appendix G).
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
• Pregnancy, lactation or plans to breastfeed during the study or within 3 months of the last dose of study intervention.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (33)

Mayo Clinic of Scottsdale

Phoenix, Arizona, 85054, United States

Location

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

USC Norris Cancer Hospital

Los Angeles, California, 90033, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

University of Chicago Pritzker School of Medicine

Chicago, Illinois, 60637, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

The John Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Memorial Sloan Kettering Cancer Center

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, 33076, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Prince of Wales Hospital

Hong Kong, Shatin, New Territories, Hong Kong

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

Osaka University Hospital

Suita-shi, Osaka, 565-0871, Japan

Location

Shizuoka Cancer Center

Nakatogari, Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

National University Hospital

Singapore, 669606, Singapore

Location

Samsung Medical Center

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

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng-Kung Uni. Hosp.

Tainan, 704, Taiwan

Location

Related Links

• Study of LY3410738 in Patients with Advanced Solid Cancer Tumors with a Change in the IDH1 or IDH2 Gene

MeSH Terms

Conditions

Cholangiocarcinoma; Chondrosarcoma; Glioma; Central Nervous System Neoplasms; Glioblastoma; Colonic Neoplasms; Breast Neoplasms; Thyroid Neoplasms; Prostatic Neoplasms; Melanoma

Interventions

Gemcitabine; Cisplatin; durvalumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Astrocytoma; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 20, 2020
• Study Start: October 1, 2020
• Primary Completion: July 17, 2023
• Study Completion: May 1, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); KR (2); AU (1); JP (5); SG (1); FR (2); HK (1); US (17); TW (2)