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MLN4924

Phase 1

Acute Myelogenous Leukemia | Small molecule | Oncology |Takeda Pharmaceutical Company Limited|Last Updated: Jun 22, 2020

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLEDBiomarker
Total Trials1
Total Enrollment64

FDA Designations

No designations recorded

Clinical trial landscape

MLN4924 · 3 trials · 3 indications

Phase 1 3
NCT02122770Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Participants With Advanced Solid TumorsAdvanced Solid Tumors
COMPLETED51 Analytics
NCT01862328Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Participants With Solid TumorsSolid Tumors
COMPLETED64 Analytics
NCT01814826Study of MLN4924 Plus Azacitidine in Treatment-naive Participants With Acute Myelogenous Leukemia (AML) Who Are 60 Years or OlderAcute Myelogenous Leukemia
COMPLETED64 Analytics
PHASE1COMPLETED
Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Participants With Advanced Solid Tumors
Advanced Solid TumorsUnlock trial analytics
PHASE1COMPLETED
Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Participants With Solid Tumors
Solid TumorsUnlock trial analytics
PHASE1COMPLETED
Study of MLN4924 Plus Azacitidine in Treatment-naive Participants With Acute Myelogenous Leukemia (AML) Who Are 60 Years or Older
Acute Myelogenous LeukemiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Fluconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Fluconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Fluconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Itraconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Itraconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Itraconazole
Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose
Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Baseline up to 30 days after the last dose of study drug (up to 5 years)

Secondary Endpoints

Part A: Plasma Clearance (CLp) for MLN4924
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
Part A Tmax: Time to Reach the Cmax for MLN4924
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
Part A: Volume of Distribution (Vz) for MLN4924
Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
MLN4924 + FluconazoleEXPERIMENTALPart A: MLN4924, 8 milligram per square meter (mg/m\^2), intravenously, once on Days 1 and 8; and fluconazole, 400 milligram (mg), tablets, orally, once on Day 4, and 200 mg, once daily on Days 5-10. Part B: MLN4924, at a dose previously deemed tolerable, given on Days 1, 3, and 5 of each 21-day Cycle (Study C15010, Clinicaltrials.gov Identifier # NCT01862328) in combination with docetaxel or carboplatin + paclitaxel at standard dose regimen on Day 1 of each 21-day Cycle.
MLN4924 + ItraconazoleEXPERIMENTALPart A: MLN4924, 8-mg/m\^2, intravenously, once on Days 1 and 8; and itraconazole, 200 mg, oral solution, once daily on Days 4-10. Part A (safety lead-in step): MLN4924, 15mg/m\^2, intravenously, once on Days 1 and 8; and itraconazole, 200 mg, oral solution, once daily on Days 4-10. Part A: MLN4924, 20mg/m\^2, intravenously, once on Days 1 and 8; and itraconazole, 200 mg, oral solution, once daily on Days 4-10. Part B: MLN4924, at a dose previously deemed tolerable given, on Days 1, 3, and 5 of each 21-day Cycle (Study C15010, ClinicalTrails.gov Identifier # NCT01862328) in combination with docetaxel or carboplatin + paclitaxel at standard dose regimen on Day 1 of each 21-day Cycle.
MLN4924 and Docetaxel (Arm 1)EXPERIMENTAL -
MLN4924 + Paclitaxel + Carboplatin (Arm 2)EXPERIMENTAL -
MLN4924 + Gemcitabine (Arm 3)EXPERIMENTAL -
MLN4924 and AzacitidineEXPERIMENTAL -

Interventions

NameTypeDescription
MLN4924DRUGMLN4924 intravenous solution.
FluconazoleDRUGFluconazole tablets.
ItraconazoleDRUGItraconazole oral solution.
DocetaxelDRUGDocetaxel intravenous solution.
CarboplatinDRUGCarboplatin intravenous solution.
PaclitaxelDRUGPaclitaxel intravenous solution.
GemcitabineDRUGGemcitabine (IV) in participants in a 28-day cycle: -Gemcitabine on Days 1,8,15 of each cycle
AzacitidineDRUGAzacitidine (IV) or subcutaneously in AML participants in a 28-day cycle: \- Azacitidine Days 1, 2, 3, 4, 5, 8, 9 in Cycle 1 and for all subsequent cycles
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites4

Inclusion Criteria: 1. Male or female participants 18 years of age or older. 2. Must have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is deemed appropriate for treatment with 1 of the 2 chemotherapy regimens in Part B of this study, or h...

Countries:United States
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Frequently asked questions about MLN4924

What is MLN4924 used for?

MLN4924 is an investigational small molecule being studied for the treatment of acute myelogenous leukemia (AML) and solid tumors, including advanced solid tumors. It is in Phase 1 clinical development and is not yet approved by the FDA.

What does MLN4924 target?

MLN4924 is a small molecule that targets the NEDD8-activating enzyme (NAE), which plays a role in protein degradation pathways. By inhibiting NAE, it disrupts cellular processes that are important for tumor growth, though specific molecular targets have not been detailed.

Who makes MLN4924?

MLN4924 is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The company is conducting Phase 1 clinical trials for this investigational drug in oncology indications.

What phase is MLN4924 in?

MLN4924 is in Phase 1 clinical development. It is an investigational drug and has not received FDA approval. All completed trials for MLN4924 are Phase 1 studies, and it remains in early-stage clinical testing.

What clinical trials is MLN4924 in?

MLN4924 has been studied in three completed Phase 1 trials: NCT01814826 for AML in patients 60 years or older, NCT01862328 for solid tumors, and NCT02122770 for advanced solid tumors. These trials were conducted in the United States.

Is MLN4924 the same as pevonedistat?

MLN4924 is also known as pevonedistat, though this alternative name has not been officially confirmed. It is an investigational small molecule being developed by Takeda for oncology indications, and it is not yet approved for any use.