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

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ClinicalTrials.gov Identifier: NCT04603001
Recruitment Status : Recruiting
First Posted : October 26, 2020
Last Update Posted : March 11, 2021
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Loxo Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE October 12, 2020
First Posted Date  ICMJE October 26, 2020
Last Update Posted Date March 11, 2021
Actual Study Start Date  ICMJE December 1, 2020
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
  • To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) [ Time Frame: Up to 30 months ]
    For Dose Escalation
  • To assess the activity of LY3410738 as measured by the overall response rate (ORR) per the investigator assessment [ Time Frame: Up to 30 months ]
    For Dose Expansion
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
  • 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 ]
    For Dose Escalation
  • To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points [ Time Frame: Up to 30 months ]
    For Dose Escalation
  • To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma [ Time Frame: Up to 30 months ]
    For Dose Escalation
  • To assess the activity of LY3410738 as measured by the overall response rate (ORR) per investigator assessment [ Time Frame: Up to 30 months ]
    For Dose Escalation
  • To assess the activity of LY3410738 as measured by Best Overall Response per investigator assessment [ Time Frame: Up to 30 months ]
    For Dose Expansion
  • To assess the activity of LY3410738 by Complete Response Rate plus partial hematologic recovery (AML patients) [ Time Frame: Up to 30 months ]
    For Dose Expansion
  • To assess the activity of LY3410738 by Duration of Response [ Time Frame: Up to 30 months ]
    For Dose Expansion
  • To assess the activity of LY3410738 by Hematologic improvement in patients with MDS [ Time Frame: Up to 30 months ]
    For Dose Expansion
  • 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 ]
    For Dose Expansion
  • To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points [ Time Frame: Up to 30 months ]
    For Dose Expansion
  • To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma. [ Time Frame: Up to 30 months ]
    For Dose Expansion
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
Official Title  ICMJE A Phase 1 Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
Brief Summary 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia (AML)
  • Myelodysplastic Syndrome (MDS)
  • Chronic Myelomonocytic Leukemia (CMML)
  • Myeloproliferative Neoplasms (MPNs)
Intervention  ICMJE Drug: LY3410738
Oral LY3410738
Study Arms  ICMJE
  • Experimental: Dose Escalation Arm A
    Patients not requiring a strong CYP3A4 inhibitor.
    Intervention: Drug: LY3410738
  • Experimental: Dose Escalation Arm B
    Patients requiring a strong CYP3A4 inhibitor for active management or prevention of a lifethreatening condition, such as an azole administered to prevent invasive fungal infection.
    Intervention: Drug: LY3410738
  • Experimental: Cohort 1
    Patients with R/R AML harboring an IDH1 R132 mutation who have received a prior IDH inhibitor.
    Intervention: Drug: LY3410738
  • Experimental: Cohort 2
    Patients with R/R AML harboring an IDH1 R132 mutation who have not received a prior IDH inhibitor.
    Intervention: Drug: LY3410738
  • Experimental: Cohort 3
    Patients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation,
    Intervention: Drug: LY3410738
  • Experimental: Cohort 4
    Patients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations.
    Intervention: Drug: LY3410738
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 21, 2020)
220
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date February 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patient Advocacy 833-LOXO-IDH clinicaltrials@loxooncology.com
Listed Location Countries  ICMJE Australia,   France,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04603001
Other Study ID Numbers  ICMJE LOXO-IDH-20001
2020-002830-33 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Loxo Oncology, Inc.
Study Sponsor  ICMJE Loxo Oncology, Inc.
Collaborators  ICMJE Eli Lilly and Company
Investigators  ICMJE
Study Director: Elizabeth Olek, DO, MPH Loxo Oncology
PRS Account Loxo Oncology, Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP