A Study of BGB-11417 in Participants With Myeloid Malignancies

Official title

A Phase 1b/2, Open-Label, Dose Finding, and Expansion Study of the Bcl-2 Inhibitor BGB-11417 in Patients With Myeloid Malignancies

Overview

The study will determine the safety, tolerability, recommended Phase 2 dose (RP2D) and preliminary efficacy of BGB-11417 as monotherapy and in combination with azacitidine in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)or MDS/myeloproliferative neoplasm (MPN) .

Detailed description

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Interventions

• Drug BGB-11417
  Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.
• Drug Azacitidine
  Intravenous or subcutaneous administration for 7 days.
• Drug Posaconazole
  Oral administration for 8 days on second cycle only.
• Drug BGB-11417
  Oral administration for 28 days on a 28-day cycle.
• Drug BGB-11417
  Oral administration for 10, 14 or 21 days on a 28-day

Primary outcome measures

• 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)]
• Part 1 And 2: Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [Time frame: Approximately 24 months]
• Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate [Time frame: Approximately 24 months]
• Part 3 MDS Cohort: Modified Overall Response (mOR) Rate [Time frame: Approximately 24 months]
• Part 3 AML Cohort (DDI Sub-cohort): Area Under Plasma Concentration-time Curve (AUC) from time 0 to the last quantifiable timepoint (t) (AUC0-t) Of BGB-11417 When Administered Alone and 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)]
• Part 3 AML Cohort (DDI Sub-cohort): Maximum Observed Plasma Concentration (Cmax) Of BGB-11417 When Administered Alone and 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)]
• 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 Administered Alone and 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)]
• Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number Of Participants Experiencing DLTs [Time frame: Cycle 2]
• Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs [Time frame: Approximately 24 months]

Secondary outcome measures (12)

• Parts 1 And 2 AML Cohort: Complete remission (CR) + Morphologic CR With Partial Hematologic Recovery (CRh) [Time frame: Approximately 24 months]
• Parts 1 And 2 MDS Cohort: mOR Rate [Time frame: Approximately 24 months]
• 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]
• Parts 1 And 2: Terminal Half-life (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]
• 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]
• 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]
• Parts 1 And 2: Apparent Total Clearance Of Azacitidine From Plasma (CL/F) When Coadministered With BGB-11417 [Time frame: Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose]
• 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]
• 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]
• 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]
• 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]
• 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]

Eligibility criteria

Inclusion criteria

• Confirmed diagnosis of one of the following by 2016 World Health Organization criteria:

• AML, nonacute promyelocytic leukemia
• MDS
• MDS/MPN
• Eastern Cooperative Oncology Group performance status of 0 to 2.
• 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
• Life expectancy of > 12 weeks.
• Ability to comply with the requirements of the study.

Exclusion criteria

• A diagnosis of acute promyelocytic leukemia.
• History of prior malignancy, with the exception of either a history of MDS or MDS/MPN that has transformed to AML, or other prior malignancy that was treated with a full curative intent and no evidence of recurrence within the past 2 years (eg, localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer)
• Antecedent MPN including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
• Prior therapy with a B-cell lymphoma-2 inhibitor
• Known central nervous system involvement by leukemia.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 12 centers

• Peking University Peoples Hospital — Beijing
• The First Hospital of Lanzhou University — Lanzhou
• Guangdong Provincial Peoples Hospital — Guangzhou
• Nanfang Hospital, Southern Medical University — Guangzhou
• The Second Peoples Hospital of Shenzhen — Shenzhen
• Henan Cancer Hospital — Zhengzhou
• Union Hospital of Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• The First Affiliated Hospital of Soochow University — Suzhou
• … and 4 more centers

Australia · 11 centers

• Concord Repatriation General Hospital — Concord
• St George Hospital — Kogarah
• Orange Health Hospital — Orange
• Gold Coast University Hospital — Southport
• Monash Health — Clayton
• St Vincents Hospital Melbourne — Fitzroy
• Austin Health — Heidelberg
• The Alfred Hospital — Melbourne
• … and 3 more centers

United States · 5 centers

• City of Hope National Medical Center — Duarte
• Tampa General Hospital — Tampa
• Upmc Hillman Cancer Center(Univ of Pittsburgh) — Pittsburgh
• Md Anderson Cancer Center — Houston
• Medical College of Wisconsin — Milwaukee

Spain · 4 centers

• Hospital de La Santa Creu I Sant Pau — Barcelona
• Hospital Universitario de Salamanca — Salamanca
• Hospital Universitario Virgen Del Rocio — Seville
• Hospital Universitari I Politecnic La Fe — Valencia

France · 3 centers

• Hopital Claude Huriez Chu Lille — Lille
• Hopital Larchet — Nice
• Hopital Saint Louis — Paris

Italy · 3 centers

• Policlinico Sorsola Malpighi, Aou Di Bologna — Bologna
• Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst — Meldola
• Niguarda Cancer Center Division of Hematology — Milan

Germany · 2 centers

• Universitaetsklinikum Leipzig Aor — Leipzig
• Universitaetsklinikum Ulm — Ulm

New Zealand · 2 centers

• North Shore Hospital — Auckland
• Wellington Regional Hospital (Ccdhb) — Wellington

South Korea · 2 centers

• Samsung Medical Center — GangnamGu
• Severance Hospital Yonsei University Health System — SeodaemunGu

United Kingdom · 2 centers

• Edinburgh Cancer Centre — Edinburgh
• The Christie Hospital — Greater Manchester

Identifiers

NCT: NCT04771130 · BGB-11417-103 · 2021-003285-12 · 2023-508881-14-00 · CTR20213416

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20213416 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗