Phase 1  | 
Enrolling
 | Investigational Drug

NCT04603001

Advanced Hematologic Malignancies

IDH1/2 Inhibitor


A Phase 1 Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations*

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Key Inclusion Criteria
  • ≥18 years of age or age of majority if higher per local regulations
  • Advanced IDH-mutant hematologic malignancy including:
    • For dose escalation arm C and dose expansion cohort 5: 
      • Patients with newly diagnosed acute myeloid leukemia (AML) who are 75 years or older or have comorbidities that preclude the use of intensive chemotherapy
      • Patients with relapsed/refractory AML (US only)
  • Patients must have received prior therapy
  • Patients must have a qualifying IDH1 R132, IDH2 R140, or IDH2 R172 mutation
  • Blasts at least 5% in bone marrow
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Adequate organ function
  • Able to swallow capsules or tablets
  • Able to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
  • Males and females of reproductive potential must be willing to use conventional and effective birth control
Key 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 study treatment
  • For dose escalation arm C and dose expansion cohort 5:
    • Prior venetoclax therapy is not permitted
    • Patients are allowed to receive up to 1 cycle of single agent azacitidine or azacitidine + 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 study treatment
  • Active, uncontrolled clinically significant systemic bacterial, viral, fungal, or parasitic infection, or an unexplained fever >101.3°F during screening or on the first day of study treatment
  • Another concurrent malignancy requiring active therapy
  • Active central nervous system involvement
  • Any unresolved toxicities from prior therapy > grade 2 as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 at the time of starting study treatment, except for alopecia
  • History of hematopoietic stem cell transplant, or CAR-T therapy within 60 days of the first dose of study treatment
  • Clinically significant cardiovascular disease 
  • Active hepatitis B or C virus
  • Known HIV, excluded due to potential drug-drug interactions between antiretroviral medications and study treatment
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitor, with the exception of patients being treated with allowed antifungal inhibitors of CYP3A4
  • Treatment with proton pump inhibitor within 7 days of starting study drug
  • Any serious underlying medical or psychiatric condition, 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
  • Pregnancy, lactation, or plan to breastfeed during the study or within 90 days of the last dose of study treatment
  • Known hypersensitivity to any components of the study drug or its formulation
*
This clinical trial is being conducted globally.
Additional criteria not shown here may exist for individual parts of the study.
LY3410738 is administered PO.
§
Venetoclax is administered PO.
Azacitidine is administered subcutaneously or intravenously.
Contact the Loxo Oncology at Lilly Clinical Trial Team

Visit www.clinicaltrials.gov for more information on this trial.

The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.