Universitaetsklinikum Leipzig Aor 04103 Leipzig (Sachsen) GermanyRekrutierend» Google-MapsCity of Hope National Medical Center 91010 Duarte United StatesRekrutierend» Google-MapsTampa General Hospital 33606 Tampa United StatesRekrutierend» Google-Maps
Maryland Oncology Hematology, Pa 21044 Columbia United StatesRekrutierend» Google-MapsUpmc Hillman Cancer Center(Univ of Pittsburgh) 15232 Pittsburgh United StatesRekrutierend» Google-MapsMd Anderson Cancer Center 77030 Houston United StatesRekrutierend» Google-MapsMedical College of Wisconsin 53226 Milwaukee United StatesRekrutierend» Google-MapsConcord Repatriation General Hospital 2139 Concord AustraliaRekrutierend» Google-MapsSt George Hospital 2217 Kogarah AustraliaRekrutierend» Google-MapsOrange Health Hospital 2800 Orange AustraliaRekrutierend» Google-MapsGold Coast University Hospital 4215 Southport AustraliaRekrutierend» Google-MapsJohn Flynn Private Hospital 4224 Tugun AustraliaRekrutierend» Google-MapsMonash Health 3168 Clayton AustraliaRekrutierend» Google-MapsSt Vincents Hospital Melbourne 3065 Fitzroy AustraliaRekrutierend» Google-MapsAustin Health 3084 Heidelberg AustraliaRekrutierend» Google-MapsThe Alfred Hospital 3004 Melbourne AustraliaRekrutierend» Google-MapsFiona Stanley Hospital 6150 Murdoch AustraliaRekrutierend» Google-MapsLinear Clinical Research 6009 Nedlands AustraliaRekrutierend» Google-MapsOne Clinical Research 6009 Nedlands AustraliaRekrutierend» Google-MapsPeking University Peoples Hospital 100044 Beijing ChinaRekrutierend» Google-MapsThe First Hospital of Lanzhou University 730000 Lanzhou ChinaRekrutierend» Google-MapsGuangdong Provincial Peoples Hospital 510080 Guangzhou ChinaRekrutierend» Google-MapsNanfang Hospital of Southern Medical University 510515 Guangzhou ChinaRekrutierend» Google-MapsThe Second Peoples Hospital of Shenzhen 518037 Shenzhen ChinaRekrutierend» Google-MapsHenan Cancer Hospital 450000 Zhengzhou ChinaRekrutierend» Google-MapsUnion Hospital of Tongji Medical College, Huazhong University of Science and Technology 430022 Wuhan ChinaRekrutierend» Google-MapsThe First Affiliated Hospital of Soochow University 215006 Suzhou ChinaRekrutierend» Google-MapsThe First Affiliated Hospital of Nanchang University Branch Donghu 330006 Nanchang ChinaRekrutierend» Google-MapsWest China Hospital, Sichuan University 610041 Chengdu ChinaRekrutierend» Google-MapsTianjin Medical University Cancer Institute and Hospital 300060 Tianjin ChinaRekrutierend» Google-MapsThe First Affiliated Hospital, Zhejiang University School of Medicine 310003 Hangzhou ChinaRekrutierend» Google-MapsSeoul National University Hospital 03080 Seoul Korea, Republic ofRekrutierend» Google-MapsSeverance Hospital Yonsei University Health System 03722 Seoul Korea, Republic ofRekrutierend» Google-MapsAsan Medical Center 05505 Seoul Korea, Republic ofRekrutierend» Google-MapsSamsung Medical Center 06351 Seoul Korea, Republic ofRekrutierend» Google-MapsNorth Shore Hospital 0622 Takapuna New ZealandRekrutierend» Google-MapsWellington Regional Hospital (Ccdhb) 6021 Wellington New ZealandRekrutierend» Google-MapsHospital de La Santa Creu I Sant Pau 08025 Barcelona SpainRekrutierend» Google-MapsHospital Universitario de Salamanca 37007 Salamanca SpainRekrutierend» Google-MapsHospital Universitario Virgen Del Rocio 41013 Sevilla SpainRekrutierend» Google-MapsHospital Universitari I Politecnic La Fe 46026 Valencia SpainRekrutierend» Google-Maps
1. Part 1 And 2: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs) (Time Frame - Cycle 1 (Up to 28 days for non-hematologic DLTs and up to 42 days for hematologic DLTs))
2. Part 1 And 2: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing Treatment-emergent Adverse Events (TEAEs) (Time Frame - Approximately 24 months)
3. Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate (Time Frame - Approximately 24 months): CR plus CRh will be defined as the proportion of participants whose best overall response (BOR) is CR plus CRh. BOR will be defined as the best response recorded from the first dose of study drug until data cut or the initiation of new anticancer treatment.
4. Part 3 MDS Cohort: Modified Overall Response (mOR) Rate (Time Frame - Approximately 24 months): The mOR will be defined as the proportion of participants whose BOR is achieving CR, marrow complete remission (mCR), or partial remission (PR) at any time point during the study for myelodysplastic/myeloproliferative neoplasm (MDS/MPN).
5. Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) from time 0 to the last quantifiable (AUC0-t) Of BGB-11417 When Co-administered With Posaconazole (Time Frame - Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose))
6. Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Coadministered With Posaconazole (Time Frame - Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 2, 4, 6, 8, and 24 hours postdose))
7. Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) from time 0 to infinity (AUC0-infinity) Of BGB-11417 When Co-administered With Posaconazole (Time Frame - Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, , 4, 6, 8, and 24 hours postdose))
8. Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs (Time Frame - Cycle 2)
9. Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs (Time Frame - Approximately 24 months)
Secondary outcome:
1. Parts 1 And 2 AML Cohort: CR Plus CRh Rate (Time Frame - Approximately 24 months)
2. Parts 1 And 2 MDS Cohort: mOR Rate (Time Frame - Approximately 24 months)
3. Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417 (Time Frame - Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose)
4. Parts 1 And 2: t1/2 Of Azacitidine When Coadministered With BGB-11417 (Time Frame - Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose)
5. Parts 1 And 2: AUC From Time Zero To Time t (AUC0-t) Of Azacitidine When Coadministered With BGB-11417 (Time Frame - Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose)
6. Parts 1 And 2: AUC From Time Zero To Infinity (AUC0-inf) Of Azacitidine When Coadministered With BGB-11417 (Time Frame - Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose)
7. Parts 1 And 2: Apparent Total Clearance Of Drug From Plasma After Oral Administration (CL/F) Of Azacitidine When Coadministered With BGB-11417 (Time Frame - Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose)
8. Parts 1 And 2: Apparent Volume Of Distribution (Vz/F) Of Azacitidine When Coadministered With BGB-11417 (Time Frame - Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose)
9. Parts 1 And 2: Steady-state AUC From Time Zero To Time Of Last Measurable Concentration (AUClast,ss) Of BGB-11417 When Coadministered With Azacitidine (Time Frame - Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose)
10. Parts 1 And 2: Steady-state Cmax (Cmax,ss) Of BGB-11417 When Coadministered With Azacitidine (Time Frame - Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose)
11. Parts 1 And 2: Steady-state Trough Plasma Concentration (Ctrough,ss) Of BGB-11417 When Coadministered With Azacitidine (Time Frame - Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose)
12. Parts 1 And 2: Steady-state Time To Maximum Observed Plasma Concentration (tmax,ss) Of BGB-11417 When Coadministered With Azacitidine (Time Frame - Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose)
13. Part 3: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing TEAEs (Time Frame - Approximately 24 months)
14. Part 3: Complete Response (Time Frame - Approximately 24 months): CR will be defined as the proportion of participants whose BOR is CR. BOR will be defined as the best response recorded from the first dose of study drug until data cut or the initiation of new anticancer treatment.
15. Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate (Time Frame - Approximately 24 months): CRi will be defined as the proportion of participants whose BOR is CRi.
16. Part 3 AML Cohort: Overall Response Rate (ORR) (Time Frame - Approximately 24 months): The ORR will include participants whose BOR include CR, CRi, PR, and morphologic leukemia-free state.
17. Part 3 AML Cohort: Duration Of Response (DOR) (Time Frame - Approximately 24 months): DOR will be defined as the time from the first response to disease progression documented after treatment initiation or death, whichever occurs first. DOR will include CR, CR plus CRi, overall response (OR), and CR plus CRh.
18. Part 3 AML Cohort: Time To Response (TTR) (Time Frame - Approximately 24 months): TTR will be defined as the time from treatment initiation to the first documented response and will include CR, CR plus CRi, OR, and CR plus CRh.
19. Part 3 AML Cohort: Event-free Survival (EFS) (Time Frame - Approximately 24 months): EFS will be defined as the time from treatment initiation to disease progression, treatment failure, relapse (hematologic relapse for AML) for those who have treatment success, or death due to any cause, whichever happens first.
20. Part 3 AML Cohort: Overall Survival (OS) (Time Frame - Approximately 24 months): OS will be defined as the time from treatment initiation to death. OS will be analyzed using the same methods as the EFS analysis except for the censoring rules.
21. Part 3 AML Cohort: Number Of Participants Receiving BGB-11417 In Combination With Posaconazole Experiencing TEAEs (Time Frame - Approximately 24 months)
22. Part 3 AML Cohort: Number of Participants with Transfusion Independence (Time Frame - Approximately 24 months): Transfusion independence will be defined as the proportion of participants whose BOR is transfusion independence. Transfusion independence will need to last for at least 56 consecutive days postbaseline.
23. Part 3 MDS Cohort: Number Of Participants With Hematological Improvement-erythroid (HI-E) (Time Frame - Approximately 24 months): The proportion of participants whose BOR is HI-E
24. Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-platelet (HI-P) (Time Frame - Approximately 24 months): The proportion of participants whose BOR is HI-P
25. Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-neutrophil (HI-N) (Time Frame - Approximately 24 months): The proportion of participants whose BOR is HI-N will be reported.
26. Part 3 MDS Cohort: Number of participants with Transfusion Independence (Time Frame - Approximately 24 months): Transfusion independence will be defined as the proportion of participants whose BOR is transfusion independence. Transfusion independence will need to last for at least 56 consecutive days postbaseline.
27. Part 3: Ctrough,ss Of BGB-11417 When Coadministered With Azacitidine (Time Frame - Cycle 1 Day 1 and Cycle 2 Day 5 (predose and 4 and 6 hours postdose))
28. Part 3 MDS cohort: Partial Hematologic Recovery CRh (Time Frame - Approximately 24 months): Proportion of participants with partial hematologic recovery will be reported
29. Part 3 AML (Treated with Monotherapy): Complete Response + Morphologic complete Remission with Partial Hematologic Recovery (Time Frame - Approximately 24 months): Proportion of participants with Complete Response + Morphologic complete Remission with Partial Hematologic Recovery will be reported.
30. Part 3 AML (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417 (Time Frame - Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose))
31. Part 3 MDS (Treated with Monotherapy): Modified Overall Response (Time Frame - Approximately 24 months): Proportion of participants with modified overall response including CR, marrow CR (mCR) or partial remission (PR)
32. Part 3 MDS (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417 (Time Frame - Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose))
Experimental: Parts 1 and 2: AML Cohorts Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle.
Experimental: Parts 1 and 2: MDS Cohorts Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.
Experimental: Part 3: AML and MDS Cohorts Participants with AML and MDS will receive BGB-11417 and azacitidine on a 28-day cycle. A subset of the participants will receive a modified second cycle of treatment to explore drug-drug interactions (DDI) with posaconazole.
Experimental: Part 3: AML and MDS Cohort Participants with MDS and R/R AML (China only) will receive BGB-11417 on a 28-day cycle.