A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies

A Phase 1b/2, Open-Label, Master Protocol Study of BTK-Degrader BGB-16673 in Combination With Other Agents in Patients With Relapsed or Refractory B-Cell Malignancies

The purpose of this study is to measure the safety, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics with BGB-16673 in combination with other agents in participants with relapsed or refractory (R/R) B-cell malignancies. This study is structured as a master protocol with separate substudies. This study currently includes four substudies, and more substudies may be added as other combination agents are identified.

Study Overview

• Status: Recruiting
• Conditions: B-cell Lymphoma; B-cell Malignancy; Relapsed Cancer; Refractory Cancer
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Sonrotoclax; Drug: Zanubrutinib; Drug: BGB-16673; Drug: Mosunetuzumab; Drug: Glofitamab

Detailed Description

This new study will check how safe and helpful a potential anticancer drug called BGB-16673 is in participants with R/R B-cell malignancies when it is given in combination with other medicines - sonrotoclax in substudy 1, zanubrutinib in substudy 2, mosunetuzumab in substudy 3, and glofitamab in substudy 4.

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 1.877.828.5568; Email: clinicaltrials@beonemed.com

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, NSW 2217
      • Recruiting
      • St George Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, QLD 4101
      • Recruiting
      • Mater Cancer Care Centre
  • Victoria
    • Clayton, Victoria, Australia, VIC 3168
      • Recruiting
      • Monash Health
    • Melbourne, Victoria, Australia, VIC 3004
      • Recruiting
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, VIC 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • Recruiting
      • Linear Clinical Research
• Brazil
  • Brasília, Brazil, 70200-730
    • Recruiting
    • Hospital Sirio Libanes Brasilia
  • Salvador, Brazil, 41950-640
    • Recruiting
    • Ensino e Terapia de Inovacao Clinica AMO Etica
  • São José do Rio Preto, Brazil, 15090-000
    • Recruiting
    • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • São Paulo, Brazil, 05652-900
    • Recruiting
    • Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat Sen University Cancer Center
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicinechengzhan
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
  • Jena, Germany, 07747
    • Recruiting
    • Universitatsklinikum Jena Klinik Fur Innere Medizin Ii
  • Kiel, Germany, 24105
    • Recruiting
    • Universitatsklinikum Schleswig Holstein, Campus Kiel
  • Tübingen, Germany, 72076
    • Recruiting
    • Medizinische Universitaetsklinik
  • Ulm, Germany, 89081
    • Recruiting
    • Universitaetsklinikum Ulm
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi
  • Milan, Italy, 20162
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Naples, Italy, 80131
    • Recruiting
    • Istituto Nazionale Tumori Fondazione G Pascale
  • Rozzano, Italy, 20089
    • Recruiting
    • Istituto Clinico Humanitas
  • Verona, Italy, 37134
    • Recruiting
    • Centroricerche Cliniche Di Verona Srl
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital
  • Auckland, New Zealand, 0622
    • Recruiting
    • North Shore Hospital
• Poland
  • Gdansk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Lublin, Poland, 20-081
    • Recruiting
    • Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie
  • Olsztyn, Poland, 10-228
    • Recruiting
    • Szpital Kliniczny Mswia Z Warmisko Mazurskim Centrum Onkologii
  • Opole, Poland, 45-061
    • Recruiting
    • Szpital Wojewodzki W Opolu Sp Z Oo Oddzia Hematologii I Onkologii Hematologicznej
  • Warsaw, Poland, 02-781
    • Recruiting
    • Narodowy Instytut Onkologii Im Marii Sklodowskiej Curie Hematology Unit
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054-4502
      • Recruiting
      • Mayo Clinic Phoenix
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California Norris Comprehensive
  • Florida
    • Jacksonville, Florida, United States, 32224-1865
      • Recruiting
      • Mayo Clinic Jacksonville
    • Tampa, Florida, United States, 33612-9496
      • Recruiting
      • Moffitt Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205-2003
      • Recruiting
      • The University of Kansas Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Recruiting
      • Mayo Clinic Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Recruiting
      • Washington University School of Medicine
  • New Jersey
    • Florham Park, New Jersey, United States, 07932-1049
      • Recruiting
      • Summit Medical Group
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
    • New York, New York, United States, 10029-6504
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10065-6800
      • Recruiting
      • Memorial Sloan Kettering Cancer Center Mskcc
    • New York, New York, United States, 10065-4870
      • Recruiting
      • Weill Cornell Medical College Newyork Presbyterian Hospital
    • Rochester, New York, United States, 14642-0001
      • Recruiting
      • University of Rochester
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2434
      • Recruiting
      • Fox Chase Cancer Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • Recruiting
      • Huntsman Cancer Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-0001
      • Recruiting
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-1222
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Must sign the informed consent form (ICF) and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the ICF
• Confirmed diagnosis of a R/R B-cell malignancy
• Protocol-defined measurable disease
• Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
• Adequate organ function
• Female participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for ≥ 7 days after the last dose of sonrotoclax, 30 days after the last dose of BGB-16673 or zanubrutinib, 60 days after the last dose of glofitamab, or 90 days after the last dose of mosunetuzumab. A negative urine or serum pregnancy test result must be provided 10-14 days before the first dose of study treatment
• Nonsterile male participants must be willing to use a highly effective method of birth control and refrain from sperm donation for the duration of the study and for ≥ 7 days after the last dose of sonrotoclax, 30 days after the last dose of BGB-16673 or zanubrutinib, 60 days after the last dose of glofitamab, or 90 days after the last dose of mosunetuzumab

• Substudies 1, 3, and 4 Inclusion Criterion:

  • Adequate renal function as indicated by estimated glomerular filtration rate (eGFR) of ≥ 50 mL/min

• Substudy 2 Inclusion Criteria:

  • Bruton tyrosine kinase (BTK) inhibitor-naive, or previously received treatment with a covalent BTK inhibitor and discontinued for reasons other than clinical progression
  • Adequate renal function as indicated by eGFR of ≥ 30 mL/min

Key Exclusion Criteria:

• Treatment-naive B-cell malignancies
• Unable to comply with the requirements of the protocol
• Active leptomeningeal disease or uncontrolled, untreated brain metastasis
• Any malignancy ≤ 2 years before first dose of study treatment except for the specific cancer under investigation in this study or any locally recurring cancer that has been treated curatively
• Autologous stem cell transplant ≤ 3 months prior to screening or chimeric antigen T-cell therapy ≤ 3 months prior to screening
• Prior invasive fungal infection, except if participant agrees to receive secondary antifungal prophylaxis during the entire treatment period
• Substudies 1 and 2: Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or who have taken calcineurin inhibitors within 4 weeks prior to consent
• Participants who have a history of severe allergic reactions or hypersensitivity to the active ingredient and excipients of BGB-16673, sonrotoclax, zanubrutinib, mosunetuzumab, or glofitamab

• Substudy 1 Exclusion Criterion:

  • Prior treatment with a B-cell lymphoma-2 (Bcl-2) inhibitor (with exception for participants who relapsed ≥ 24 months after completion of a full course of a prior Bcl-2 inhibitor containing regimen)

• Substudy 2 Exclusion Criterion:

  • Participants who discontinued prior zanubrutinib treatment due to intolerance

• Substudies 3 and 4 Exclusion Criteria:

  • Prior exposure to a CD20 x CD3 T-cell engager antibody treatment
  • All participants with a prior allogeneic stem cell transplant
  • Participants with known contraindications to azole antifungal agents, including hypersensitivity reactions

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

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Substudy 1 Part 1a: Dose Escalation; Sequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies.	Drug: Sonrotoclax; Administered orally; Other Names: BGB-11417; Drug: BGB-16673; Administered orally
Experimental: Substudy 1 Part 1b: Safety Expansion; Cohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies.	Drug: Sonrotoclax; Administered orally; Other Names: BGB-11417; Drug: BGB-16673; Administered orally
Experimental: Substudy 2 Part 1a: Dose Escalation; Sequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies.	Drug: Zanubrutinib; Administered orally; Drug: BGB-16673; Administered orally
Experimental: Substudy 2 Part 1b: Safety Expansion; Cohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies.	Drug: Zanubrutinib; Administered orally; Drug: BGB-16673; Administered orally
Experimental: Substudy 3 Part 1a: Dose Escalation; Sequential cohorts of increasing dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies.	Drug: BGB-16673; Administered orally; Drug: Mosunetuzumab; Administered subcutaneously
Experimental: Substudy 3 Part 1b: Safety Expansion; Cohorts of select dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies.	Drug: BGB-16673; Administered orally; Drug: Mosunetuzumab; Administered subcutaneously
Experimental: Substudy 4 Part 1a: Dose Escalation; Sequential cohorts of increasing dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies. Participants will receive obinutuzumab as pretreatment prior to the start of combination treatment.	Drug: Obinutuzumab; Administered intravenously; Drug: BGB-16673; Administered orally; Drug: Glofitamab; Administered intravenously
Experimental: Substudy 4 Part 1b: Safety Expansion; Cohorts of select dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies.	Drug: Obinutuzumab; Administered intravenously; Drug: BGB-16673; Administered orally; Drug: Glofitamab; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Substudy 1 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 1 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 2 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 2 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 3 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 3 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years]
Substudy 4 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Substudy 4 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Substudy 1 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and sonrotoclax		From Week 1 to Week 17
Substudy 1 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and sonrotoclax		From Week 1 to Week 17
Substudy 1 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and sonrotoclax		From Week 1 to Week 17
Substudy 1 Part 1a: Terminal half-life (t1/2) of BGB-16673 and sonrotoclax		From Week 1 to Week 17
Substudy 1 Part 1b: Number of patients with complete response or complete response with incomplete count recovery (CR/CRi) who achieve undetectable minimal residual disease (uMRD)		Up to approximately 3 years
Substudy 2 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and zanubrutinib		From Week 1 to Week 17
Substudy 2 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and zanubrutinib		From Week 1 to Week 17
Substudy 2 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and zanubrutinib		From Week 1 to Week 17
Substudy 2 Part 1a: Terminal half-life (t1/2) of BGB-16673 and zanubrutinib		From Week 1 to Week 17
Substudy 1 Parts 1a and 1b: Overall Response Rate (ORR) in participants with B-cell malignancies	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by investigator.	Up to approximately 3 years
Substudy 1 Parts 1a and 1b: Duration of Response (DOR)	DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.	Up to approximately 3 years
Substudy 1 Parts 1a and 1b: Time to Response (TTR)	TTR is defined as the time from treatment initiation to first documented response.	Up to approximately 3 years
Substudy 1 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and sonrotoclax		From Week 1 to Week 17
Substudy 2 Parts 1a and 1b: ORR in participants with B-cell malignancies	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator.	Up to approximately 3 years
Substudy 2 Parts 1a and 1b: DOR	DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.	Up to approximately 3 years
Substudy 2 Parts 1a and 1b: TTR	TTR is defined as the time from treatment initiation to the first documented response.	Up to approximately 3 years
Substudy 2 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and zanubrutinib		From Week 1 to Week 17 for Part 1a; From Week 1 to Week 5 for Part 1b
Substudy 3 Parts 1a and 1b: ORR in participants with B-cell malignancies	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator.	Up to approximately 3 years
Substudy 3 Parts 1a and 1b: DOR	DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.	Up to approximately 3 years
Substudy 3 Parts 1a and 1b: TTR	TTR is defined as the time from treatment initiation to the first documented response.	Up to approximately 3 years
Substudy 3 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and mosunetuzumab		From Week 1 to Week 12
Substudy 3 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and mosunetuzumab		From Week 1 to Week 12
Substudy 3 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and mosunetuzumab		From Week 1 to Week 12
Substudy 3 Part 1a: Terminal half-life (t1/2) of BGB-16673 and mosunetuzumab		From Week 1 to Week 12
Substudy 3 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and mosunetuzumab		From Week 1 to Week 36
Substudy 4 Parts 1a and 1b: ORR in participants with B-cell malignancies	ORR is defined as the percentage of participants with partial response (PR) or better as assessed by the investigator.	Up to approximately 3 years
Substudy 4 Parts 1a and 1b: DOR	DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.	Up to approximately 3 years
Substudy 4 Parts 1a and 1b: TTR	TTR is defined as the time from treatment initiation to the first documented response.	Up to approximately 3 years
Substudy 4 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673		From Week 1 to Week 10
Substudy 4 Part 1a: Maximum observed concentration (Cmax) of BGB-16673		From Week 1 to Week 10
Substudy 4 Part 1a: Time to maximum concentration (Tmax) of BGB-16673		From Week 1 to Week 10
Substudy 4 Part 1a: Terminal half-life (t1/2) of BGB-16673		From Week 1 to Week 10
Substudy 4 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673		From Week 1 to Week 10

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2024
• Primary Completion (Estimated): December 2, 2028
• Study Completion (Estimated): December 2, 2029

Study Registration Dates

• First Submitted: October 8, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: B-cell lymphoma; zanubrutinib; Mosunetuzumab; Bruton Tyrosine Kinase (BTK); Glofitamab; sonrotoclax; R/R B-Cell Malignancies; relapsed or refractory B-Cell Malignancies; B-Cell malignancy; BGB-16673
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Neoplasms; Recurrence; Lymphoma, B-Cell; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib; obinutuzumab; glofitamab
• Other Study ID Numbers: BGB-16673-104; 2024-516234-35-00 (Ctis); CTR20244676 (Registry Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

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

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No