This Phase I trial is seeking to determine the recommended dose level, safety and effectiveness of a targeted therapy (LY3410738) in people with IDH-mutant advanced blood cancers (including acute myeloid leukaemia, myelodysplastic syndrome, chronic myelomonocytic leukaemia and myeloproliferative neoplasms) who have previously received standard therapyA Phase 1 Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations

Exclusion

• 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
• Treatment with proton pump inhibitor (PPIs) within 7 days of starting LY3410738
• Any serious underlying medical or psychiatric condition (e.g. alcohol or drug abuse), 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
• Known human immunodeficiency virus (HIV), excluded due to potential drug-drug interactions between antiretroviral medications and LY3410738
• Pregnancy, lactation or plan to breastfeeding during the study or within 90 days of the last dose of study intervention
• Known hypersensitivity to any of the components of LY3410738 or its formulation