A Study of BGB-11417 in Participants With Myeloid Malignancies

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

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) .

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm
• Intervention / Treatment: Drug: Azacitidine; Drug: BGB-11417; Drug: BGB-11417; Drug: Posaconazole; Drug: BGB-11417

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: 1.877.828.5568; Email: clinicaltrials@beigene.com

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • St George Hospital
    • Orange, New South Wales, Australia, 2800
      • Recruiting
      • Orange Health Hospital
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • Gold Coast University Hospital
    • Tugun, Queensland, Australia, 4224
      • Recruiting
      • John Flynn Private Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St Vincents Hospital Melbourne
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Recruiting
      • Fiona Stanley Hospital
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research
• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University Peoples Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Recruiting
      • The First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Guangdong Provincial Peoples Hospital
    • Shenzhen, Guangdong, China, 518037
      • Recruiting
      • The Second Peoples Hospital of Shenzhen
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
• Germany
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitaetsklinikum Leipzig Aor
• Korea, Republic of
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
      • Recruiting
      • Seoul National University Hospital
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
      • Recruiting
      • Samsung Medical Center
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Recruiting
      • Severance Hospital Yonsei University Health System
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 05505
      • Recruiting
      • Asan Medical Center
• New Zealand
  • Takapuna, New Zealand, 0622
    • Recruiting
    • North Shore Hospital
  • Wellington, New Zealand, 6021
    • Recruiting
    • Wellington Regional Hospital (Ccdhb)
• Spain
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Universitario de Salamanca
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politecnic La Fe
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
  • Florida
    • Tampa, Florida, United States, 33606
      • Recruiting
      • Tampa General Hospital
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Recruiting
      • Maryland Oncology Hematology, PA
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • Upmc Hillman Cancer Center(Univ of Pittsburgh)
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

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

   • AML, nonacute promyelocytic leukemia
   • MDS
   • MDS/MPN
2. Eastern Cooperative Oncology Group performance status of 0 to 2.

3. 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
4. Life expectancy of > 12 weeks.
5. Ability to comply with the requirements of the study.

Key Exclusion Criteria:

1. A diagnosis of acute promyelocytic leukemia.
2. 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.
3. Antecedent MPN including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
4. Prior therapy with a B-cell lymphoma-2 inhibitor or azacitidine except for participants who meet HMA-failure criteria
5. Known central nervous system involvement by leukemia.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parts 1 and 2: AML Cohorts; Participants with AML will receive BGB-11417 and azacitidine on a 28-day cycle.	Drug: Azacitidine; Intravenous or subcutaneous administration for 7 days.; Drug: BGB-11417; Oral administration for 28 days on a 28-day cycle.; Drug: BGB-11417; Oral administration for 10 or 21 days on a 28-day; Drug: BGB-11417; Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.; Other Names: Sonrotoclax
Experimental: Parts 1 and 2: MDS Cohorts; Participants with MDS will receive BGB-11417 and azacitidine on a 28-day cycle.	Drug: Azacitidine; Intravenous or subcutaneous administration for 7 days.; Drug: BGB-11417; Oral administration for 28 days on a 28-day cycle.; Drug: BGB-11417; Oral administration for 10 or 21 days on a 28-day; Drug: BGB-11417; Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.; Other Names: Sonrotoclax
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.	Drug: Azacitidine; Intravenous or subcutaneous administration for 7 days.; Drug: BGB-11417; Oral administration for 28 days on a 28-day cycle.; Drug: BGB-11417; Oral administration for 10 or 21 days on a 28-day; Drug: Posaconazole; Oral administration for 8 days on second cycle only.; Drug: BGB-11417; Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.; Other Names: Sonrotoclax
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.	Drug: BGB-11417; Oral administration for 28 days on a 28-day cycle.; Drug: BGB-11417; Oral administration for 10 or 21 days on a 28-day; Drug: BGB-11417; Oral administration for 10, 21, 14 or 28 days on a 28-day cycle.; Other Names: Sonrotoclax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 And 2: Number Of Participants Experiencing Dose-limiting Toxicities (DLTs)		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 Receiving BGB-11417 In Combination With Azacitidine Experiencing Treatment-emergent Adverse Events (TEAEs)		Approximately 24 months
Part 3 AML Cohort: Complete Remission (CR) Plus CR With Partial Hematologic Recovery (CRh) Rate	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.	Approximately 24 months
Part 3 MDS Cohort: Modified Overall Response (mOR) Rate	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).	Approximately 24 months
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		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 Coadministered With Posaconazole		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 Co-administered With Posaconazole		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		Cycle 2
Part 3 AML and MDS Cohorts (Treated with Monotherapy): Number of Participants Experiencing TEAEs		Approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1 And 2 AML Cohort: CR Plus CRh Rate		Approximately 24 months
Parts 1 And 2 MDS Cohort: mOR Rate		Approximately 24 months
Parts 1 And 2: Cmax Of Azacitidine When Coadministered With BGB-11417		Day 0 and 4 (Cycle 1) predose and at multiple time points up to 4 hours postdose
Parts 1 And 2: t1/2 Of Azacitidine When Coadministered With BGB-11417		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		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		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 Drug From Plasma After Oral Administration (CL/F) Of Azacitidine When Coadministered With BGB-11417		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		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		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		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		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		Day 1-4 and 28 (Cycle 1) Day 5 (Cycle 2) predose and at multiple time points up to 8 hours postdose
Part 3: Number Of Participants Receiving BGB-11417 In Combination With Azacitidine Experiencing TEAEs		Approximately 24 months
Part 3: Complete Response	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.	Approximately 24 months
Part 3 AML Cohort: CR With Incomplete Hematologic Recovery (CRi) Rate	CRi will be defined as the proportion of participants whose BOR is CRi.	Approximately 24 months
Part 3 AML Cohort: Overall Response Rate (ORR)	The ORR will include participants whose BOR include CR, CRi, PR, and morphologic leukemia-free state.	Approximately 24 months
Part 3 AML Cohort: Duration Of Response (DOR)	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.	Approximately 24 months
Part 3 AML Cohort: Time To Response (TTR)	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.	Approximately 24 months
Part 3 AML Cohort: Event-free Survival (EFS)	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.	Approximately 24 months
Part 3 AML Cohort: Overall Survival (OS)	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.	Approximately 24 months
Part 3 AML Cohort: Number Of Participants Receiving BGB-11417 In Combination With Posaconazole Experiencing TEAEs		Approximately 24 months
Part 3 AML Cohort: Number of Participants with Transfusion Independence	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.	Approximately 24 months
Part 3 MDS Cohort: Number Of Participants With Hematological Improvement-erythroid (HI-E)	The proportion of participants whose BOR is HI-E	Approximately 24 months
Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-platelet (HI-P)	The proportion of participants whose BOR is HI-P	Approximately 24 months
Part 3 MDS Cohort: Proportion Of Participants With Hematological Improvement-neutrophil (HI-N)	The proportion of participants whose BOR is HI-N will be reported.	Approximately 24 months
Part 3 MDS Cohort: Number of participants with Transfusion Independence	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.	Approximately 24 months
Part 3: Ctrough,ss Of BGB-11417 When Coadministered With Azacitidine		Cycle 1 Day 1 and Cycle 2 Day 5 (predose and 4 and 6 hours postdose)
Part 3 MDS cohort: Partial Hematologic Recovery CRh	Proportion of participants with partial hematologic recovery will be reported	Approximately 24 months
Part 3 AML (Treated with Monotherapy): Complete Response + Morphologic complete Remission with Partial Hematologic Recovery	Proportion of participants with Complete Response + Morphologic complete Remission with Partial Hematologic Recovery will be reported.	Approximately 24 months
Part 3 AML (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417		Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose)
Part 3 MDS (Treated with Monotherapy): Modified Overall Response	Proportion of participants with modified overall response including CR, marrow CR (mCR) or partial remission (PR)	Approximately 24 months
Part 3 MDS (Treated with Monotherapy): Steady State trough plasma concentration of BGB-11417		Cycle 2 Day 12 and Cycle 2 Day 20 (predose and 1, 4, 6, 8, and 24 hours postdose)

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: February 23, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: AML; Posaconazole; MDS; Azacitidine; MDS/MPN; BGB-11417
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Azacitidine; Posaconazole
• Other Study ID Numbers: BGB-11417-103; 2021-003285-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No