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

Official title

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

Overview

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.

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.

Interventions

• Drug BGB-16673
  Administered orally
• Drug Sonrotoclax
  Administered orally
• Drug Zanubrutinib
  Administered orally
• Drug Mosunetuzumab
  Administered subcutaneously
• Drug Glofitamab
  Administered intravenously
• Drug Obinutuzumab
  Administered intravenously

Primary outcome measures

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

Secondary outcome measures (12)

• Substudy 1 Parts 1a and 1b: Overall Response Rate (ORR) in participants with B-cell malignancies [Time frame: Up to approximately 3 years]
• Substudy 1 Parts 1a and 1b: Duration of Response (DOR) [Time frame: Up to approximately 3 years]
• Substudy 1 Parts 1a and 1b: Time to Response (TTR) [Time frame: Up to approximately 3 years]
• Substudy 1 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and sonrotoclax [Time frame: From Week 1 to Week 17]
• Substudy 1 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and sonrotoclax [Time frame: From Week 1 to Week 17]
• Substudy 1 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and sonrotoclax [Time frame: From Week 1 to Week 17]
• Substudy 1 Part 1a: Terminal half-life (t1/2) of BGB-16673 and sonrotoclax [Time frame: From Week 1 to Week 17]
• Substudy 1 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and sonrotoclax [Time frame: 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) [Time frame: Up to approximately 3 years]
• Substudy 2 Parts 1a and 1b: ORR in participants with B-cell malignancies [Time frame: Up to approximately 3 years]
• Substudy 2 Parts 1a and 1b: DOR [Time frame: Up to approximately 3 years]
• Substudy 2 Parts 1a and 1b: TTR [Time frame: Up to approximately 3 years]

Eligibility criteria

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

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.

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

United States · 18 centers

• Mayo Clinic Phoenix — Phoenix
• University of Southern California Norris Comprehensive — Los Angeles
• Mayo Clinic Jacksonville — Jacksonville
• Moffitt Cancer Center — Tampa
• The University of Kansas Cancer Center — Westwood
• Mayo Clinic Rochester — Rochester
• Washington University School of Medicine — St Louis
• Summit Medical Group — Florham Park
• … and 10 more centers

Australia · 6 centers

• St George Hospital — Kogarah
• Mater Cancer Care Centre — South Brisbane
• Monash Health — Clayton
• Peter Maccallum Cancer Centre — Melbourne
• The Alfred Hospital — Melbourne
• Linear Clinical Research — Nedlands

China · 5 centers

• Fujian Medical University Union Hospital — Fuzhou
• Sun Yat Sen University Cancer Center — Guangzhou
• The First Affiliated Hospital of Soochow University — Suzhou
• The First Affiliated Hospital, Zhejiang University School of Medicinechengzhan — Hangzhou
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Germany · 5 centers

• Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden — Dresden
• Universitatsklinikum Jena Klinik Fur Innere Medizin Ii — Jena
• Universitatsklinikum Schleswig Holstein Campus Kiel — Kiel
• Medizinische Universitaetsklinik — Tübingen
• Universitaetsklinikum Ulm — Ulm

Italy · 5 centers

• Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi — Bologna
• Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda — Milan
• Istituto Nazionale Tumori Fondazione G Pascale — Naples
• Istituto Clinico Humanitas — Rozzano
• Centroricerche Cliniche Di Verona Srl — Verona

Poland · 5 centers

• Uniwersyteckie Centrum Kliniczne — Gdansk
• Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie — Lublin
• Szpital Kliniczny Mswia Z Warmisko Mazurskim Centrum Onkologii — Olsztyn
• Szpital Wojewodzki W Opolu Sp Z Oo Oddzia Hematologii I Onkologii Hematologicznej — Opole
• Narodowy Instytut Onkologii Im Marii Sklodowskiej Curie W Warszawie — Warsaw

Brazil · 4 centers

• Hospital Sirio Libanes Brasilia — Brasília
• Ensino E Terapia de Inovacao Clinica Amo Etica — Salvador
• Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto — São José do Rio Preto
• Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein — São Paulo

New Zealand · 2 centers

• North Shore Hospital — Auckland
• Auckland City Hospital — Auckland

Identifiers

NCT: NCT06634589 · BGB-16673-104 · 2024-516234-35-00 · CTR20244676

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20244676 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗