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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04603001




Registration number
NCT04603001
Ethics application status
Date submitted
12/10/2020
Date registered
26/10/2020

Titles & IDs
Public title
Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
Scientific title
A Phase 1 Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
Secondary ID [1] 0 0
2020-002830-33
Secondary ID [2] 0 0
LOXO-IDH-20001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia (AML) 0 0
Myelodysplastic Syndrome (MDS) 0 0
Chronic Myelomonocytic Leukemia (CMML) 0 0
Myeloproliferative Neoplasms (MPNs) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY3410738
Treatment: Drugs - Venetoclax
Treatment: Drugs - Azacitidine

Experimental: Dose Escalation Arm A (Monotherapy) - Patients not requiring a strong cytochrome P450 3A4 (CYP3A4) inhibitor.

Experimental: Dose Escalation Arm B (Monotherapy) - 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.

Experimental: Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine) - Patients with no prior venetoclax therapy and not requiring a strong CYP3A4 inhibitor for active treatment within 7 days of starting LY3410738.

Experimental: Cohort 1 - Patients with relapsed/refractory (R/R) AML harboring an IDH1 R132 mutation who have received a prior IDH inhibitor.

Experimental: Cohort 2 - Patients with R/R AML harboring an IDH1 R132 mutation who have not received a prior IDH inhibitor.

Experimental: Cohort 3 - Patients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation.

Experimental: Cohort 4 - Patients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations.

Experimental: Cohort 5 - Patients with newly diagnosed AML, R/R AML, or other advanced hematologic malignancy harboring IDH1 and/or IDH2 mutations with no prior venetoclax therapy. Strong CYP3A4 inhibitor allowed but not required.


Treatment: Drugs: LY3410738
Oral LY3410738

Treatment: Drugs: Venetoclax
Oral venetoclax

Treatment: Drugs: Azacitidine
Subcutaneous or intravenous azacitidine
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
Timepoint [1] 0 0
Up to 30 months
Primary outcome [2] 0 0
To assess the activity of LY3410738 as measured by the overall response rate (ORR) per the Investigator assessment
Timepoint [2] 0 0
Up to 30 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to 30 months
Secondary outcome [2] 0 0
To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
Timepoint [2] 0 0
Up to 30 months
Secondary outcome [3] 0 0
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma
Timepoint [3] 0 0
Up to 30 months
Secondary outcome [4] 0 0
To assess the activity of LY3410738 as measured by the overall response rate (ORR) per Investigator assessment
Timepoint [4] 0 0
Up to 30 months
Secondary outcome [5] 0 0
To assess the activity of LY3410738 as measured by Best Overall Response (BOR) per Investigator assessment
Timepoint [5] 0 0
Up to 30 months
Secondary outcome [6] 0 0
To assess the activity of LY3410738 by Complete Remission (CR) Rate (CRR) plus partial hematologic recovery (AML patients)
Timepoint [6] 0 0
Up to 30 months
Secondary outcome [7] 0 0
To assess the activity of LY3410738 by Duration of Response
Timepoint [7] 0 0
Up to 30 months
Secondary outcome [8] 0 0
To assess the activity of LY3410738 by Hematologic improvement in patients with MDS
Timepoint [8] 0 0
Up to 30 months
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Up to 30 months
Secondary outcome [10] 0 0
To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
Timepoint [10] 0 0
Up to 30 months
Secondary outcome [11] 0 0
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma.
Timepoint [11] 0 0
Up to 30 months

Eligibility
Key inclusion criteria
* Advanced IDH mutant hematologic malignancy including:

-- For Dose Escalation Arm C and Dose Expansion Cohort 5:
* Patients with newly diagnosed AML who are 75 years or older or have comorbidities that preclude the use of intensive chemotherapy
* Patients with R/R AML (US only)
* 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 to 2
* Adequate organ function
* Ability to swallow capsules or tablets
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2025
Actual
Sample size
Target
260
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Belgium
State/province [9] 0 0
Brussels
Country [10] 0 0
Canada
State/province [10] 0 0
British Columbia
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Finland
State/province [13] 0 0
Helsinki
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
France
State/province [16] 0 0
Pessac Cedex
Country [17] 0 0
France
State/province [17] 0 0
Pierre Benite Cedex
Country [18] 0 0
France
State/province [18] 0 0
Toulouse cedex 9
Country [19] 0 0
Germany
State/province [19] 0 0
Niedersachsen
Country [20] 0 0
Israel
State/province [20] 0 0
Haifa
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul-teukbyeolsi [Seoul]
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Singapore
State/province [23] 0 0
Singapore
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid
Country [26] 0 0
Spain
State/province [26] 0 0
Valencia
Country [27] 0 0
Taiwan
State/province [27] 0 0
Taichung City
Country [28] 0 0
Taiwan
State/province [28] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04603001