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CholangiocarcinomaPhase 1NCT04521686

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

A Phase 1 study testing LY3410738, Gemcitabine and Cisplatin in people with Cholangiocarcinoma and Chondrosarcoma, run by Eli Lilly and Company at 33 sites in 9 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cholangiocarcinoma, Chondrosarcoma, Glioma
What is being tested?
LY3410738, Gemcitabine and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
33 sitesin 9 countries
Study dates
1 Oct 2020to May 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Measurable disease as determined by RECIST 1.1.
  • Monotherapy Dose Expansion Cohort 2:
  • A locally advanced or metastatic solid tumor (except for cholangiocarcinoma), where standard curative or palliative measures are no longer effective or are not considered appropriate or safe in the opinion of the investigator.
  • Measurable disease as determined by RECIST 1.1 or RANO as appropriate by tumor types.
  • Monotherapy Dose Expansion Cohort 3:
  • 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.
  • Non-measurable disease only as determined by RECIST 1.1 or RANO as appropriate by tumor type.
  • Combination Dose Expansion Cohort 4:
  • Histologically or cytologically confirmed diagnosis of advanced or metastatic cholangiocarcinoma, not eligible for curative resection.
  • No prior systemic therapy for advanced or metastatic disease with the following exceptions:
  • Patients who received adjuvant chemotherapy are eligible, if the adjuvant therapy was completed at least 6 months prior to the development of advanced or metastatic disease.
  • Patients who are receiving up to two cycles of cisplatin plus gemcitabine as the first line systemic therapy while waiting for results of molecule profiling including IDH1/IDH2 mutational status, are eligible, provided that a radiographic assessment during screening demonstrates the absence of interval disease progression since initiation of chemotherapy treatment, and all other eligibility criteria are met.
  • Measurable disease as determined by RECIST 1.1.
  • Combination Dose Expansion Cohort 5:
  • Cholangiocarcinoma patients with IDH1 R132, IDH2 R140, or IDH2 R172 mutations
  • Histologically or cytologically confirmed diagnosis of advanced or metastatic cholangiocarcinoma, following 1 or more lines of prior systemic treatment for advanced disease.
  • Measurable disease as determined by RECIST 1.1

Who cannot join

  • 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
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  • 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.
  • Active second malignancy unless in remission and with life expectancy > 2 years. Refer to protocol exclusion criteria (Section 4.2) for examples of allowed second malignancies.
  • Pregnancy, lactation or plans to breastfeed during the study or within 3 months of the last dose of study intervention.
  • Patients with known hypersensitivity to any component of LY3410738 or its formulation.
  • Combination Dose Expansion Cohort 5:
  • Prior treatment with anti-PD 1 or anti-PD L1 therapies.
  • History of Grade 3 or higher immune-related adverse events (irAEs).
  • Active autoimmune disease that has required systemic anti-autoimmune treatment in the past 2 years.
  • Endocrine replacement therapy is not considered a form of systemic therapy and is allowed.
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids which should not exceed 10 mg/day of prednisone or equivalent corticosteroid.
  • Active interstitial lung disease or history of noninfectious pneumonitis Grade 2 or higher that required treatment with systemic corticosteroids or immunosuppressive drugs.
  • History of hypersensitivity to durvalumab or any excipient.
  • Has received a live vaccine within 30 days prior to the first dose of study drug.

Trial locations and contacts

33 sites in 9 countries.

33 sites in 9 countries

United States17 sites

  • The John Hopkins Hospital

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • University of Chicago Pritzker School of Medicine

    Chicago, Illinois, 60637

  • Memorial Sloan Kettering Cancer Center

    Commack, New York, 11725

  • Memorial Sloan Kettering Cancer Center

    Harrison, New York, 10604

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224

  • USC Norris Cancer Hospital

    Los Angeles, California, 90033

  • Memorial Sloan Kettering Cancer Center

    Middletown, New Jersey, 07748

  • Sarah Cannon Cancer Center

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic of Scottsdale

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55902

  • South Texas Accelerated Research Therapeutics, LLC

    San Antonio, Texas, 78229

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85724

Other trials in United States

Japan5 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Cancer Center Hospital East

    Kashiwa, Chiba, 277-8577

  • Shizuoka Cancer Center

    Nakatogari, Shizuoka, 411-8777

  • Osaka University Hospital

    Suita-shi, Osaka, 565-0871

  • Kanagawa Cancer Center

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

France2 sites

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

    Bordeaux, 33076

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

South Korea2 sites

  • Samsung Medical Center

    Seoul, Seoul-teukbyeolsi [Seoul], 06351

  • Seoul National University Hospital

    Seoul, 03080

Other trials in South Korea

Spain2 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

Other trials in Spain

Taiwan2 sites

  • China Medical University Hospital

    Taichung, 40447

  • National Cheng-Kung Uni. Hosp.

    Tainan, 704

Other trials in Taiwan

Australia1 site

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

Other trials in Australia

Hong Kong1 site

  • Prince of Wales Hospital

    Hong Kong, Shatin, New Territories

Other trials in Hong Kong

Singapore1 site

  • National University Hospital

    Singapore, 669606

Other trials in Singapore

About this study

Official title: A Phase 1 Study of LY3410738 Administered to Patients With Advanced Solid Tumors With IDH1 or IDH2 Mutations

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.

Read the detailed description

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

This study includes 2 parts: Phase 1 dose escalation and Phase 1 dose expansion. The Phase 1 dose escalation monotherapy cohort will enroll any eligible patient with IDH1 R132-mutant advanced solid tumor or IDH1 or IDH2 mutant cholangiocarcinoma. The Phase 1 dose expansion will include 5 cohorts to further evaluate safety and clinical activity. Three cohorts will be administered LY3410738 monotherapy. The fourth cohort will administer LY3410738 at or below the monotherapy RP2D in combination with gemcitabine and cisplatin. The fifth cohort (US only) will administer LY3410738 at or below the monotherapy RP2D in combination with durvalumab.

IDH1 R132, IDH2 R140, or IDH2 R172 mutations will be identified through genomic testing utilizing material collected prior to patient consent. Molecular assays utilized for enrollment are required to be performed in CLIA, ISO/IEC, CAP, or other similarly certified laboratory. Enrollment of patients with cholangiocarcinoma, chondrosarcoma or glioma may be made based on molecular tests performed in either tumor or blood. Enrollment of patients with other tumor types is limited to testing performed in tumor tissue.

Being tested
LY3410738, Gemcitabine, Cisplatin, Durvalumab
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
Medical subject headings
Cholangiocarcinoma, Chondrosarcoma, Glioma, Central Nervous System Neoplasms, Glioblastoma, Colonic Neoplasms, Breast Neoplasms, Thyroid Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LY3410738Drug

    Oral LY3410738

  • GemcitabineDrug

    Also called LY188011

    Intravenous gemcitabine

  • CisplatinDrug

    Intravenous cisplatin

  • DurvalumabDrug

    Intravenous durvalumab

Study groups in NCT04521686
Study groupRoleWhat they receive
LY3410738ExperimentalPhase 1 dose escalation - Multiple doses of LY3410738
Receives: Drug: LY3410738
LY3410738 alone or in combination with gemcitabine and cisplatin or in combination with durvalumabExperimentalPhase 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
Receives: Drug: LY3410738; Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended Phase 2 Dose (RP2D)

    Measured: Up to 24 months

Secondary outcomes (5)

  1. Objective Response Rate

    Measured: Up to 24 months

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

    Measured: Up to 24 months

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

    Measured: Up to 24 months

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

    Measured: Up to 24 months

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

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2020
  2. Study start1 Oct 2020
  3. Primary completion17 Jul 2023
  4. Study completionMay 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04521686
Sponsor's protocol ID
18077
Other IDs
2020-002863-77, I9Y-OX-JDHC, LOXO-IDH-20002
Status last verified
Jul 2026
First submitted
13 Aug 2020
Last updated
22 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LY3410738, Gemcitabine and Cisplatin in people with Cholangiocarcinoma and Chondrosarcoma, run by Eli Lilly and Company at 33 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Japan, France, South Korea, Spain and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase 2 Dose (RP2D) (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04521686.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.

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