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Pevonedistat /m^2

Phase 1

Leukemia, Myeloid, Acute | Small molecule | Oncology |Takeda Pharmaceutical Company Limited|Last Updated: Nov 3, 2023

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment23
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02782468A Study of Pevonedistat in Adult East Asian ParticipantsPHASE1 COMPLETED 23 — — May 16, 2016Jan 25, 2022Nov 3, 20239 Japan, South Korea +1
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Study Endpoints
Primary Endpoints
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
From first dose through 30 days after the last dose of study drug: single agent arms (up to Cycle 19 [up to Day 429]) (Cycle=21 days); combination arms (up to Cycle 65 [up to Day 1850]) (Cycle=28 days)
Number of Participants With Dose Limiting Toxicities (DLTs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 During Cycle 1
Cycle 1 (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

DLT: Any of following events considered possibly related to study drug(s) by investigator: Grade (G) 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis; G3 diarrhea occurred despite maximal supportive therapy; G3 arthralgia/myalgia despite use of optimal analgesia; G3 nonhematologic toxicity with exceptions: 1) Brief fatigue, 2) hypophosphatemia; Persistent elevations of transaminases/bilirubin above G2 beyond 2 days between doses; Other study drug-related nonhematologic toxicities G2 or greater, required a dose reduction/discontinuation of pevonedistat. G3 or greater hematologic toxicities, including G3 or 4 febrile neutropenia, considered DLTs if: A delay in initiation of Cycle 2 due to lack of adequate recovery from treatment-related toxicity: 1) Of more than (\>) 4 weeks due to hematologic toxicity believed not related to leukemic infiltration. Bone marrow (BM) evaluation may have been required. 2) Of \>2 weeks due to nonhematologic toxicities.

Number of Participants With Clinically Significant Abnormal Laboratory Values
Baseline up to Cycle 19 (up to Day 399) in single agent arms (Cycle=21days) and Cycle 65 (up to Day 1820) in combination arms (Cycle=28 days)
Cmax: Maximum Observed Plasma Concentration for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 1
Cycle 1 Day 1: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])
Cmax: Maximum Observed Plasma Concentration for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5
Cycle 1 Day 5: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])
AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5
Cycle 1 Day 5: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])
CL: Total Clearance for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 1
Cycle 1 Day 1: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])
CL: Total Clearance for Pevonedistat When Administered Alone and in Combination With Azacitidine on Cycle 1 Day 5
Cycle 1 Day 5: pre-infusion and at multiple time points (up to 48 hours) post-infusion (Cycle length = 21 days [single agent arms]; 28 days [combination arms])
Secondary Endpoints
Overall Response Rate (ORR) for Participants With AML
From first dose up to 30 days after last dose of study drug or before start of subsequent antineoplastic therapy, whichever comes earlier up to Cycle 19 (up to Day 429, single agent)(Cycle=21 days) and Cycle 65 (up to Day 1850, combination)(Cycle=28 days)
ORR for Participants With MDS
From first dose up to 30 days after last dose of study drug or before start of subsequent antineoplastic therapy, whichever comes earlier up to Cycle 19 (up to Day 429, single agent)(Cycle=21 days) and Cycle 65 (up to Day 1850, combination)(Cycle=28 days)
Percentage of Participants With CR for Participants With AML
From first dose up to 30 days after last dose of study drug or before start of subsequent antineoplastic therapy, whichever comes earlier up to Cycle 19 (up to Day 429, single agent)(Cycle=21 days) and Cycle 65 (up to Day 1850, combination)(Cycle=28 days)
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Arm 1, Cohort 1: Pevonedistat 25 mg/m^2EXPERIMENTALPevonedistat, 25 milligram per square meter (mg/m\^2), 60-minute infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in 21-day treatment cycles.
Arm 1, Cohort 2: Pevonedistat 44 mg/m^2EXPERIMENTALPevonedistat, 44 mg/m\^2, 60-minute infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in 21-day treatment cycles.
Arm 2, Cohort 1: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2EXPERIMENTALPevonedistat 10 mg/m\^2, 60-minute infusion, intravenously, on Days 1, 3, and 5 and azacitidine 75 mg/m\^2, on Days 1 to 5, and Days 8 and 9, intravenously or subcutaneously, followed by a rest period of 19 days, in 28-day treatment cycles.
Arm 2, Cohort 2: Pevonedistat 20 mg/m^2+ Azacitidine 75 mg/m^2EXPERIMENTALPevonedistat 20 mg/m\^2, 60-minute infusion, intravenously, on Days 1, 3, and 5 and azacitidine 75 mg/m\^2, on Days 1 to 5, and Days 8 and 9, intravenously or subcutaneously, followed by a rest period of 19 days, in 28-day treatment cycles.
Interventions
NameTypeDescription
Pevonedistat 25 mg/m^2DRUGPevonedistat 25 mg/m\^2 intravenous infusion.
Pevonedistat 44 mg/m^2DRUGPevonedistat 44 mg/m\^2 intravenous infusion.
Pevonedistat 10 mg/m^2DRUGPevonedistat 10 mg/m\^2 intravenous infusion.
Pevonedistat 20 mg/m^2DRUGPevonedistat 20 mg/m\^2 intravenous infusion.
Azacitidine 75 mg/m^2DRUGAzacitidine 75 mg/m\^2 intravenous or subcutaneous formulation.
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites9

Inclusion Criteria include, in part: 1. East Asian patients aged 18 years or older (or minimum age of legal consent consistent with local regulations) when written study informed consent is obtained must meet 1 of the following diagnosis criteria for either the Single-Agent Arm or the Combination A...

Countries:JapanSouth KoreaTaiwan
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