Clinical Trial Details

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

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Trial Information

Broad Health Condition Cholangiocarcinoma
Chondrosarcoma
Glioma
Any Solid Tumor

Specific Health Condition




Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,

Hospital
St Vincent's Hospital

Phase of TrialPhase 1

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 130 (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.
Eligibility

Key inclusion criteria

Inclusion Criteria:

    1. 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
       routinely 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.

    2. 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.

    3. Eastern Cooperative Oncology Group (ECOG) 0-1

    4. At least 18 years of age

    5. Adequate organ function

    6. Ability to swallow capsules or tablets

    7. Ability to comply with outpatient treatment, laboratory monitoring, and required
       clinic visits for the duration of study participation

    8. For cholangiocarcinoma patients, must have adequate biliary drainage (per
       investigator's discretion), with no evidence of ongoing infection.

    9. 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.

       Monotherapy Dose Escalation:

   10. 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.

   11. Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as
       appropriate by tumor type.

   12. Prior IDH1 inhibitor treatment is permitted.

       Monotherapy Dose Expansion Cohort 1:

   13. 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.

   14. Measurable disease as determined by RECIST 1.1.

       Monotherapy Dose Expansion Cohort 2:

   15. 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.

   16. Measurable disease as determined by RECIST 1.1 or RANO as appropriate by tumor types.

       Monotherapy Dose Expansion Cohort 3:

   17. 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.

   18. Non-measurable disease only as determined by RECIST 1.1 or RANO as appropriate by
       tumor type.

       Combination Dose Expansion Cohort 4:

   19. Histologically or cytologically confirmed diagnosis of advanced or metastatic
       cholangiocarcinoma, not eligible for curative resection.

   20. 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 the first cycle of cisplatin plus gemcitabine as the
            first line systemic therapy while waiting for results of locally obtained
            molecule profiling including IDH1 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.

   21. Measurable disease as determined by RECIST 1.1.

  Exclusion Criteria:

    1. Had an investigational agent or anticancer therapy within 2 weeks; or investigational
       monoclonal antibody within 4 weeks prior to planned start of LY3410738.

    2. Had major surgery within 4 weeks prior to planned start of LY3410738.

    3. 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.

    4. 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.

    5. 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.

    6. 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

    7. Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2
       at the time of starting study treatment except for alopecia.

    8. Have clinically significant, uncontrolled cardiac, cardiovascular disease or history
       of myocardial infarction within 6 months prior to planned start of study treatment.

    9. 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.

   10. 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).

   11. Known active hepatitis C virus (HCV). Note: Untreated patients with chronic infection
       by HCV are allowed on study. In addition, successfully treated patients (defined as
       sustained virologic response SVR12 or SVR24) are allowed, as long as there is 4 weeks
       between achieving sustained viral response (SVR12 or SVR24) and starting study drug.

   12. Known human immunodeficiency virus (HIV); excluded due to potential drug-drug
       interactions between anti-retroviral medications and LY3410738.

   13. Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
       inducers (Appendix F) and/or P-gp inhibitors (Appendix G).

   14. Treatment with proton pump inhibitor (PPIs) within 7 days of starting LY3410738
       (Appendix H). For recommended alternatives, refer to Section 6.4.3.

   15. Clinically significant active malabsorption syndrome or other condition likely to
       affect gastrointestinal absorption of the study drug.

   16. 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.

   17. Pregnancy, lactation or plans to breastfeed during the study or within 3 months of the
       last dose of study intervention.

   18. Patients with known hypersensitivity to any component of LY3410738 or its formulation.

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No

Contact details and further information

Sponsor Primary Sponsor Type: Commercial sector/Industry
Primary Sponsor Name: Eli Lilly and Company

Trial websitehttps://clinicaltrials.gov/show/NCT04521686

Trial IDNCT04521686