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

Summary

The purpose of this study is to measure the safety, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics with tacabrutideg 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.

Eligibility

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 tacabrutideg 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 tacabrutideg 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 tacabrutideg, 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.

Conditions5

Interventions7

Locations17 sites

Find trials near these locations

Related trials

• Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader — BeiGene
• A Dose-Escalation and Expansion Study of Tacabrutideg (BGB-16673) in Participants With B-Cell Malignancies — BeOne Medicines
• A Study to Evaluate the Safety and Efficacy of Tacabrutideg (BGB-16673) Compared to Pirtobrutinib in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma — BeOne Medicines
• A Study of Tacabrutideg (BGB-16673) Compared to Investigator's Choice in Participants With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Both Bruton Tyrosine Kinase (BTK) and B-cell Leukemia/Lymphoma 2 Protein (BCL2) Inhibitors — BeOne Medicines
• A Phase 2 Trial of GlOfitamab anD pIrtobrutinib in Mantle Cell Lymphoma Patients With Prior BTK Inhibitor Exposure. — Australasian Leukaemia and Lymphoma Group
• An Observational Study of Glofitamab in Chinese Adult Participants With 2L Diffuse Large B-Cell Lymphoma — Hoffmann-La Roche
• Feasibility Trial of Glofitamab in a Response Adapted Approach Incorporating Interim FDG PET and ctDNA to Optimize Primary Therapy of DLBCL (GRAIL) — University Health Network, Toronto
• Glofitamab Combined With Lenalidomide in High Risk Patients With Relapsed or Refractory Mantle Cell Lymphoma — Peking University Third Hospital

Browse More Trials