N-[4-({[(1R,4R)-4-HYDROXY-4-METHYLCYCLOHEXYL]METHYL}AMINO)-3- NITROBENZENE-1-SULFONYL]-4-(2-{(2S)-2-[2-(PROPAN-2-YL)PHENYL]PYRROLIDIN1-YL}-7-AZASPIRO[3.5]NONAN-7-YL)-2-[(1H-PYRROLO[2,3-B]PYRIDIN-5- YL)OXY]BENZAMIDE for Myeloid malignancies | Acute myeloid leukemia | Myelodysplastic syndromes | Myelodysplastic syndrome/myeloproliferative neoplasm

Inclusion criteria

• {"criterion_text":"- Confirmed diagnosis of one of the following by 2016 World Health Organization criteria: • acute myeloid leukemia (AML), nonacute promyelocytic leukemia; • myelodysplastic syndrome (MDS); or • myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN)."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2."}
• {"criterion_text":"- Adequate organ function defined as: • Creatinine clearance ≥ 50 milliliters/minute (mL/min) (or between 30 and 49 mL/min in unfit AML cohort) • Adequate liver function"}
• {"criterion_text":"- Life expectancy of > 12 weeks."}
• {"criterion_text":"- Ability to comply with the requirements of the study."}
• {"criterion_text":"- Note: other protocol-defined inclusion criteria may apply."}

Exclusion criteria

• {"criterion_text":"- A diagnosis of acute promyelocytic leukemia."}
• {"criterion_text":"- Prior malignancy within the past 2 years, except for curatively treated localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer."}
• {"criterion_text":"- Antecedent MPN including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation."}
• {"criterion_text":"- Prior therapy with a B-cell lymphoma-2 inhibitor or azacitidine except for participants who meet HMA-failure critera."}
• {"criterion_text":"- Known central nervous system involvement by leukemia."}
• {"criterion_text":"- Note: other protocol-defined exclusion criteria may apply."}

Primary endpoints

• {"endpoint_text":"- Part 1 (dose regimen finding) and Part 2 (safety expansion) • Safety and tolerability of BGB-11417 in combination with azacitidine as assessed by dose-limiting toxicities (DLTs)and the incidence, timing, and severity of treatment-emergent adverse events (TEAEs), according to NCI-CTCAE v5.0.","definition_or_measurement_approach":"Assessment of dose-limiting toxicities (DLTs) and incidence, timing, and severity of treatment-emergent adverse events (TEAEs) per NCI-CTCAE v5.0."}
• {"endpoint_text":"- Part 3 (efficacy expansion) • For AML: - complete remission (CR) + complete remission with partial hematologic recovery (CRh) rate; - In the DDI cohort: PK endpoints of BGB-11417, including but not limited to area under the curve (AUC) and maximum plasma concentration (Cmax), derived from the plasma concentration-time profiles","definition_or_measurement_approach":"AML efficacy: rates of CR + CRh. DDI cohort: PK endpoints (AUC, Cmax) derived from plasma concentration–time profiles."}
• {"endpoint_text":"- • For MDS: modified overall response (mOR) rate, including CR, marrow complete remission (mCR), and partial remission (PR).","definition_or_measurement_approach":"MDS efficacy: modified overall response (mOR) rate defined as CR, mCR, or PR as specified."}

Secondary endpoints

• {"endpoint_text":"- Part 1 (dose regimen finding) and Part 2 (safety expansion) For AML: • CR + morphologic complete remission with partial hematologic recovery (CRh) rate. For MDS: • Modified overall response (mOR) rate. mOR is defined as achieving a CR, marrow complete remission (mCR), or partial remission (PR) at any time point during the study per modified IWG 2006 criteria for MDS/MPN (Cheson et al 2006)","definition_or_measurement_approach":"AML: CR + CRh rate. MDS: mOR per modified IWG 2006 criteria (CR, mCR, PR)."}
• {"endpoint_text":"- Secondary pharmacokinetic (PK) endpoints for both AML and MDS: • Derived PK parameters, including: − For azacitidine: maximum observed plasma concentration (Cmax), area under plasma concentration-time curve (AUC0-t, AUC0-∞), half-life (t1/2), apparent total clearance of drug from plasma (CL/F), and apparent volume of distribution (Vz/F) as appropriate; − For BGB-11417: AUClast,ss, Cmax,ss, steady-state trough plasma concentration (Ctrough,ss) and tmax,ss.","definition_or_measurement_approach":"Derived PK parameters for azacitidine and BGB-11417 (Cmax, AUC, t1/2, CL/F, Vz/F, AUClast,ss, Cmax,ss, Ctrough,ss, tmax,ss) from plasma concentration–time data."}
• {"endpoint_text":"- Part 3 (efficacy expansion) For AML: • CR rate; • CR + CR with incomplete hematologic recovery (CRi) rate; • ORR (CR + CRi + PR + morphologic leukemia-free state [MLFS]); • Duration of response of CR, CR + CRi, OR and CR + CRh; • Time to response (TTR) of CR, CR + CRi, OR and CR + CRh; • Event-free survival (EFS); • Overall survival (OS). • Transfusion independence (for at least consecutive 56-day postbaseline)","definition_or_measurement_approach":"AML efficacy measures: CR, CR+CRi, ORR (CR+CRi+PR+MLFS), durations of response, time-to-response, EFS, OS, and transfusion independence (≥56 consecutive days)."}
• {"endpoint_text":"- Part 3 (efficacy expansion) For MDS: • CR rate; • Hematological improvement – erythroid (HI-E), as per IWG 2018 criteria; • Hematological improvement – platelet (HI-P), as per IWG 2018 criteria; • Hematological improvement – neutrophil (HI-N), as per IWG 2018 criteria; • Transfusion independence (for at least consecutive 56-day post-baseline); • EFS; • OS.","definition_or_measurement_approach":"MDS efficacy measures: CR, HI-E, HI-P, HI-N per IWG 2018, transfusion independence (≥56 days), EFS, OS."}
• {"endpoint_text":"- Safety endpoints for both AML and MDS: • Safety and tolerability of BGB-11417 in combination with azacitidine or posaconazole as assessed by the incidence, timing, and severity of TEAEs, according to NCI-CTCAE v5.0.","definition_or_measurement_approach":"Safety assessed by incidence, timing and severity of TEAEs per NCI-CTCAE v5.0."}

Methods

• K1_Recruitment arrangements / site-based recruitment via participating hospital hematology departments (documents labelled 'K1_Recruitment arrangements' and multiple site ICFs indicate site-centred recruitment).
• GP letters (documents 'L2_GP Letter Part 1/2/3') to primary care physicians to inform/identify potential participants.
• Scout recruitment vendor methods (documents 'SCOUT', 'Scout Email', 'Scout Telephone consent', 'Scout Pass') — outreach via email, telephone contact and telephone consent workflows and patient-facing materials.

Germany

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

31-10-2025

Processing Time Days

623

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

29-10-2025

Processing Time Days

621

Number Of Sites

4

Number Of Participants

30

Italy

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

29-10-2025

Processing Time Days

621

Number Of Sites

3

Number Of Participants

7

France

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

31-10-2025

Processing Time Days

623

Number Of Sites

3

Number Of Participants

6

Primary sponsor

Full Name

BeOne Medicines AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

code 12

Name

PPD (UK) Limited

Responsibilities

Pharmacovigilance (code 15); code 8

Third parties

• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Inivata Limited","duties_or_roles":"code 15 - BCLC2 IHC and CD34 IHC","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code 12","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Burning Rock Dx LLC","duties_or_roles":"code 15 - storage of Future Research samples","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"NeoGenomics Europe SA","duties_or_roles":"code 15 - BCL2 IHC and CD34 IHC","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Predicine Inc.","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"China","full_name":"Wuxi Apptec Co. Ltd.","duties_or_roles":"code 15 - Pharmacokinetics","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Sequanta Technologies Co. Ltd.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"code 15 - Patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"code 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"PPD (UK) Limited","duties_or_roles":"code 15 - Pharmacovigilance; code 8","organisation_type":"Pharmaceutical company"}