A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies
Purpose
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.
Conditions
- B-cell Malignancy
- Relapsed Cancer
- Refractory Cancer
- B-cell Lymphoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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 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 sonrotoclax or 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 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 sonrotoclax or 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 - 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 Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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. |
|
|
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. |
|
|
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. |
|
|
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. |
|
|
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. |
|
|
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. |
|
|
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. |
|
Recruiting Locations
Moffitt Cancer Center
Tampa, Florida 33612-9496
Tampa, Florida 33612-9496
Washington University School of Medicine
Saint Louis, Missouri 63110-1010
Saint Louis, Missouri 63110-1010
Summit Medical Group
Florham Park, New Jersey 07932-1049
Florham Park, New Jersey 07932-1049
Weill Cornell Medical College Newyork Presbyterian Hospital
New York, New York 10065-4870
New York, New York 10065-4870
Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111-2434
Philadelphia, Pennsylvania 19111-2434
The University of Texas Md Anderson Cancer Center
Houston, Texas 77030-4009
Houston, Texas 77030-4009
More Details
- NCT ID
- NCT06634589
- Status
- Recruiting
- Sponsor
- BeiGene
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.