Clinical Trials /

Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations

NCT04603001

Description:

This is an open-label, multi-center Phase 1 study of LY3410738, an oral, covalent IDH inhibitor, in patients with IDH1 or IDH2-mutant advanced hematologic malignancies who have received standard therapy

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
  • Official Title: A Phase 1 Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations

Clinical Trial IDs

  • ORG STUDY ID: LOXO-IDH-20001
  • SECONDARY ID: 2020-002830-33
  • NCT ID: NCT04603001

Conditions

  • Acute Myeloid Leukemia (AML)
  • Myelodysplastic Syndrome (MDS)
  • Chronic Myelomonocytic Leukemia (CMML)
  • Myeloproliferative Neoplasms (MPNs)

Interventions

DrugSynonymsArms
LY3410738Cohort 1

Purpose

This is an open-label, multi-center Phase 1 study of LY3410738, an oral, covalent IDH inhibitor, in patients with IDH1 or IDH2-mutant advanced hematologic malignancies who have received standard therapy

Detailed Description

      This study includes 2 parts: dose escalation and dose expansion. The dose escalation will
      enroll eligible patients with select IDH-mutant advanced hematologic malignancies. Once the
      maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of LY3410738 is
      established, the dose expansion will begin and enroll into 4 cohorts to further evaluate
      safety and clinical activity
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Arm AExperimentalPatients not requiring a strong CYP3A4 inhibitor.
  • LY3410738
Dose Escalation Arm BExperimentalPatients requiring a strong CYP3A4 inhibitor for active management or prevention of a lifethreatening condition, such as an azole administered to prevent invasive fungal infection.
  • LY3410738
Cohort 1ExperimentalPatients with R/R AML harboring an IDH1 R132 mutation who have received a prior IDH inhibitor.
  • LY3410738
Cohort 2ExperimentalPatients with R/R AML harboring an IDH1 R132 mutation who have not received a prior IDH inhibitor.
  • LY3410738
Cohort 3ExperimentalPatients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation,
  • LY3410738
Cohort 4ExperimentalPatients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations.
  • LY3410738

Eligibility Criteria

        Inclusion Criteria:

          -  Advanced IDH mutant hematologic malignancy

          -  Patients must have received prior therapy

          -  Blasts at least 5% in bone marrow.

          -  Patients must have a qualifying IDH1 R132, IDH2 R140 or IDH2 R172 mutation

          -  Eastern Cooperative Oncology Group (ECOG) 0-2

          -  Adequate organ function

          -  Ability to swallow capsules

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

          -  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.

        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 LY3410738

          -  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 CAR-T therapy within 60 days
             of the first dose of LY3410738

          -  Clinically significant cardiovascular disease

          -  Active hepatitis B (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 strong 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 anti-retroviral medications and LY3410738

          -  Pregnancy, lactation or plan to breastfeeding during the study or within 30 days of
             the last dose of study intervention

          -  Known hypersensitivity to any of the components of LY3410738 or its formulation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Escalation

Secondary Outcome Measures

Measure:To determine the safety profile and tolerability of LY3410738 including acute and chronic toxicities by collecting and evaluating adverse events and treatment emergent adverse events
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Escalation
Measure:To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Escalation
Measure:To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Escalation
Measure:To assess the activity of LY3410738 as measured by the overall response rate (ORR) per investigator assessment
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Escalation
Measure:To assess the activity of LY3410738 as measured by Best Overall Response per investigator assessment
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Expansion
Measure:To assess the activity of LY3410738 by Complete Response Rate plus partial hematologic recovery (AML patients)
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Expansion
Measure:To assess the activity of LY3410738 by Duration of Response
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Expansion
Measure:To assess the activity of LY3410738 by Hematologic improvement in patients with MDS
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Expansion
Measure:To determine the safety profile and tolerability of LY3410738 including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Expansion
Measure:To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Expansion
Measure:To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma.
Time Frame:Up to 30 months
Safety Issue:
Description:For Dose Expansion

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Loxo Oncology, Inc.

Trial Keywords

  • Loxo
  • LY3410738
  • isocitrate dehydrogenase
  • IDH
  • IDH1
  • IDH2
  • R132
  • R140
  • R172
  • 2-hydroxyglutarate
  • 2-HG
  • Advanced Hematologic Malignancies
  • Blasts
  • Acute Myeloid Leukemia
  • AML
  • Relapsed/refractory AML
  • R/R AML
  • Myelodysplastic Syndrome
  • MDS
  • Chronic Myelomonocytic Leukemia
  • CMML
  • Myeloproliferative Neoplasms
  • MPN
  • Advanced Hematologic Cancers
  • Ivosidenib
  • AG-120
  • Vorasidenib
  • AG-881
  • Olutasidenib
  • FT-2102
  • BAY1436032
  • DS-1001
  • IDH-305
  • Enasidenib
  • AG-221

Last Updated

October 21, 2020