Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Pevonedistat/m^2 · 1 trial · 2 indications
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.
| Arm | Type | Description |
|---|---|---|
| Arm 1, Cohort 1: Pevonedistat 25 mg/m^2 | EXPERIMENTAL | Pevonedistat, 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^2 | EXPERIMENTAL | Pevonedistat, 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^2 | EXPERIMENTAL | Pevonedistat 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^2 | EXPERIMENTAL | Pevonedistat 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. |
| Name | Type | Description |
|---|---|---|
| Pevonedistat 25 mg/m^2 | DRUG | Pevonedistat 25 mg/m\^2 intravenous infusion. |
| Pevonedistat 44 mg/m^2 | DRUG | Pevonedistat 44 mg/m\^2 intravenous infusion. |
| Pevonedistat 10 mg/m^2 | DRUG | Pevonedistat 10 mg/m\^2 intravenous infusion. |
| Pevonedistat 20 mg/m^2 | DRUG | Pevonedistat 20 mg/m\^2 intravenous infusion. |
| Azacitidine 75 mg/m^2 | DRUG | Azacitidine 75 mg/m\^2 intravenous or subcutaneous formulation. |
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...
Pevonedistat is an investigational small molecule being studied for the treatment of advanced solid tumors, acute myeloid leukemia (AML), myelodysplastic syndromes, refractory acute lymphoblastic leukemia, and other neoplasms. It is developed by Takeda Pharmaceutical Company Limited (TAK) and is currently in Phase 2 clinical development for these oncology indications.
Pevonedistat is a small molecule that targets NEDD8-activating enzyme (NAE), inhibiting the neddylation pathway. This disruption affects the degradation of proteins involved in cell cycle regulation and survival, which may lead to anti-tumor activity. The exact mechanism is under investigation in clinical trials.
Pevonedistat is developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. Takeda is conducting clinical trials to evaluate the drug's safety and efficacy in various oncology indications, including acute myeloid leukemia and myelodysplastic syndromes.
Pevonedistat is in Phase 2 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Completed trials include Phase 1 and Phase 3 studies, but the most advanced ongoing development is at Phase 2 for acute myeloid leukemia and other conditions.
Pevonedistat has been studied in several clinical trials, including NCT02782468, a Phase 1 study in East Asian participants with AML and myelodysplastic syndromes; NCT03268954, a Phase 3 trial comparing pevonedistat plus azacitidine to azacitidine alone; NCT03330106, a Phase 1 QT interval study; and NCT04266795, a Phase 2 trial combining pevonedistat with venetoclax and azacitidine in AML.
Pevonedistat is also known by the code name TAK-924. This alternative name is used in some clinical and research contexts to refer to the same investigational drug developed by Takeda Pharmaceutical Company Limited.