Acute Myeloid Leukemia (AML)Phase 1NCT04603001
Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
A Phase 1 study testing LY3410738, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by Eli Lilly and Company at 37 sites in 12 countries.
Trial summary
This is an open-label, multi-center Phase 1 study of LY3410738, an oral, covalent isocitrate dehydrogenase (IDH) inhibitor, in patients with IDH1 and/or IDH2-mutant advanced hematologic malignancies who may have received standard therapy Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)
- What is being tested?
- LY3410738, Venetoclax and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- 37 sitesin 12 countries
- Study dates
- 19 Nov 2020to May 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
37 sites in 12 countries.
37 sites in 12 countries
United States12 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Roswell Park Cancer Institute
Buffalo, New York, 14263-0002
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Northwestern University
Chicago, Illinois, 60611
University of Chicago Hospital
Chicago, Illinois, 60637
City of Hope National Medical Center
Duarte, California, 91010
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
UCLA Medical Center
Los Angeles, California, 90095
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of California, Davis - Health Systems
Sacramento, California, 95817
H Lee Moffitt Cancer Center
Tampa, Florida, 33612-9497
France5 sites
Institut Paoli-Calmettes
Marseille, 13273
Hopital Saint Louis
Paris, 75010
Centre hospitalier universitaire de Haut Leveque
Pessac, 33604
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Institut Claudius Regaud
Toulouse, 31059
Australia3 sites
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
The Alfred Hospital
Melbourne, Victoria, 3004
Linear Clinical Research
Nedlands, Western Australia, 6009
Canada3 sites
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Princess Margaret Hospital
Toronto, Ontario, M5G2M9
BC Cancer Vancouver
Vancouver, British Columbia, V5Z 4E6
South Korea3 sites
Asan Medical Center
Seoul, Seoul-teukbyeolsi [Seoul], 05505
Samsung Medical Center
Seoul, Seoul-teukbyeolsi [Seoul], 06351
Seoul National University Hospital
Seoul, 03080
Spain3 sites
Clinico Y Provincial Barcelona
Barcelona, 8036
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Universitario La Fe de Valencia
Valencia, 46026
Singapore2 sites
National University Cancer Institute
Singapore, 119228
Singapore General Hospital
Singapore, 169608
Taiwan2 sites
China Medical University Hospital
Taichung, 40447
National Taiwan University Hospital
Taipei, 10002
Finland1 site
Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
Helsinki, 00290
About this study
Official title: A Phase 1 Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
This is an open-label, multi-center Phase 1 study of LY3410738, an oral, covalent isocitrate dehydrogenase (IDH) inhibitor, in patients with IDH1 and/or IDH2-mutant advanced hematologic malignancies who may have received standard therapy
Read the 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 5 cohorts to further evaluate safety and clinical activity
- Conditions
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), Myeloproliferative Neoplasms (MPNs)
- Being tested
- LY3410738, Venetoclax, Azacitidine
- 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
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3410738Drug
Oral LY3410738
VenetoclaxDrug
Oral venetoclax
AzacitidineDrug
Subcutaneous or intravenous azacitidine
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Arm A (Monotherapy) | Experimental | Patients not requiring a strong cytochrome P450 3A4 (CYP3A4) inhibitor. Receives: Drug: LY3410738 |
| Dose Escalation Arm B (Monotherapy) | Experimental | 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. Receives: Drug: LY3410738 |
| Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine) | Experimental | Patients with no prior venetoclax therapy and not requiring a strong CYP3A4 inhibitor for active treatment within 7 days of starting LY3410738. Receives: Drug: LY3410738; Drug: Venetoclax; Drug: Azacitidine |
| Cohort 1 | Experimental | Patients with relapsed/refractory (R/R) AML harboring an IDH1 R132 mutation who have received a prior IDH inhibitor. Receives: Drug: LY3410738 |
| Cohort 2 | Experimental | Patients with R/R AML harboring an IDH1 R132 mutation who have not received a prior IDH inhibitor. Receives: Drug: LY3410738 |
| Cohort 3 | Experimental | Patients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation. Receives: Drug: LY3410738 |
| Cohort 4 | Experimental | Patients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations. Receives: Drug: LY3410738 |
| Cohort 5 | Experimental | 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. Receives: Drug: LY3410738; Drug: Venetoclax; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
For Dose Escalation
Measured: Up to 30 months
To assess the activity of LY3410738 as measured by the overall response rate (ORR) per the Investigator assessment
For Dose Expansion
Measured: Up to 30 months
Secondary outcomes (11)
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
For Dose Escalation
Measured: Up to 30 months
To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
For Dose Escalation
Measured: Up to 30 months
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma
For Dose Escalation
Measured: Up to 30 months
To assess the activity of LY3410738 as measured by the overall response rate (ORR) per Investigator assessment
For Dose Escalation
Measured: Up to 30 months
To assess the activity of LY3410738 as measured by Best Overall Response (BOR) per Investigator assessment
For Dose Expansion
Measured: Up to 30 months
To assess the activity of LY3410738 by Complete Remission (CR) Rate (CRR) plus partial hematologic recovery (AML patients)
For Dose Expansion
Measured: Up to 30 months
To assess the activity of LY3410738 by Duration of Response
For Dose Expansion
Measured: Up to 30 months
To assess the activity of LY3410738 by Hematologic improvement in patients with MDS
For Dose Expansion
Measured: Up to 30 months
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
For Dose Expansion
Measured: Up to 30 months
To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
For Dose Expansion
Measured: Up to 30 months
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma.
For Dose Expansion
Measured: Up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2020
- Study start19 Nov 2020
- Primary completion3 Jul 2023
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04603001
- Sponsor's protocol ID
- 18076
- Other IDs
- 2020-002830-33, I9Y-OX-JDHB, LOXO-IDH-20001
- Status last verified
- Jul 2026
- First submitted
- 12 Oct 2020
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No