A Study of Pevonedistat in Adult East Asian Participants

Time frame: 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])

Population: PK evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and pevonedistat concentration-time data to reliably estimate PK parameters by noncompartmental analysis methods and who had not received any excluded concomitant medications per the protocol. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Time frame: 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])

Population: PK evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and pevonedistat concentration-time data to reliably estimate PK parameters by noncompartmental analysis methods and who had not received any excluded concomitant medications per the protocol.

Time frame: 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])

Population: PK evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and pevonedistat concentration-time data to reliably estimate PK parameters by noncompartmental analysis methods and who had not received any excluded concomitant medications per the protocol. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Time frame: 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])

Population: Pharmacokinetic (PK) evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and pevonedistat concentration-time data to reliably estimate PK parameters by noncompartmental analysis methods and who had not received any excluded concomitant medications per the protocol.

Time frame: 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])

Population: PK evaluable population was defined as all enrolled participants who had sufficient dosing in Cycle 1 and pevonedistat concentration-time data to reliably estimate PK parameters by noncompartmental analysis methods and who had not received any excluded concomitant medications per the protocol. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

Time frame: 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)

Population: Safety population was defined as all enrolled participants who received at least 1 dose of any study drug, pevonedistat or azacitidine.

Time frame: 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)

Population: Safety population was defined as all enrolled participants who received at least 1 dose of any study drug, pevonedistat or azacitidine.

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.

Time frame: Cycle 1 (Cycle length = 21 days [single agent arms]; 28 days [combination arms])

Population: The DLT evaluable population was defined as all participants who either experienced DLT during Cycle 1 or received all scheduled doses of study drug during Cycle 1 without DLT.

ORR for MDS: Percentage of participants with CR,PR or hematologic improvement(HI) based on IWG Response Criteria. CR: BM:\<=5% myeloblasts with normal maturation of all cell lines; persistent dysplasia noted peripheral blood: hemoglobin (Hgb)\>=11 gram per deciliter (g/dL),platelets\>=100\*10\^9/L,neutrophils \>=1.0\*10\^9/L, blasts 0%. PR:CR criteria if abnormal before treatment except: BM blasts decreased by \>=50% from pretreatment but still\>5%; cellularity, morphology not relevant. HI criteria: Erythroid response:Hgb up by \>=1.5 g/dL; transfused RBC reduced by at least 4 red blood cell (RBC) transfusions/8 weeks comparatively last 8 weeks; Platelet response: Increase of \>=30\*10\^9/L for participants starting with \>20\*10\^9/L platelets; increase from \<20\*10\^9/L to \>20\*10\^9/L and by 100%; Neutrophil response: At least 100% and absolute increase \>0.5\*10\^9/L; Progression/relapse after HI: Granulocytes/platelets decreased by 50% from maximum; Hgb reduced by \>=1.5 g/dL; transfusion dependence.

Time frame: 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)

Population: Response evaluable population was defined as all participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

ORR for AML was defined as the percentage of participants with a complete remission (CR), CR with incomplete blood count recovery (CRi), or partial remission (PR) based on Modified International Working Group (IWG) Response Criteria for AML. CR was defined as participant achieved the morphologic leukemia-free state and had an absolute neutrophil count (ANC) of more than 1,000 per microliter (/mcL) and platelets of greater than or equal to (\>=) 100,000/mcL. A morphologic leukemia-free state requires less than (\<) 5 percent (%) blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. CRi was, after chemotherapy, some participants who fulfilled all of the criteria for CR except for residual neutropenia (\<1,000/mcL) or thrombocytopenia (\<100,000/mcL). PR designation required all the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to between 5% and 25% in the bone marrow aspirate.

Time frame: 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)

Population: Response evaluable population was defined as all participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

CR was defined as participant achieved the morphologic leukemia-free state and had an ANC of more than 1,000/mcL and platelets of \>=100,000/mcL. A morphologic leukemia-free state requires \<5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. CR assessment was based on IWG Response Criteria.

Time frame: 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)

Population: Response evaluable population was defined as all participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.

CR was defined as participant with bone marrow: less than or equal to (\<=) 5% myeloblasts with normal maturation of all cell lines; persistent dysplasia was noted peripheral blood: Hgb \>=11 g/dL, platelets \>=100\*10\^9/L, neutrophils \>=1.0\*10\^9 per liter (/L), blasts 0%. CR assessment was based on IWG Response Criteria.

Time frame: 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)

Population: Response evaluable population was defined as all participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Here, overall number of participants analyzed signifies those participants who were evaluable for this outcome measure.