B-cell Malignancy, Relapsed Cancer, Refractory Cancer, B-cell Lymphoma
Conditions
Keywords
R/R B-Cell Malignancies, relapsed or refractory B-Cell Malignancies, B-Cell malignancy, BGB-16673, sonrotoclax, zanubrutinib, B-cell lymphoma, Bruton Tyrosine Kinase (BTK), Mosunetuzumab, Glofitamab
Brief summary
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
DRUGBGB-16673
Administered orally
DRUGSonrotoclax
Administered orally
DRUGZanubrutinib
Administered orally
DRUGMosunetuzumab
Administered subcutaneously
DRUGGlofitamab
Administered intravenously
DRUGObinutuzumab
Administered intravenously
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 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 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 * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 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 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 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Substudy 1 Part 1a: Terminal half-life (t1/2) of BGB-16673 and sonrotoclax | From Week 1 to Week 17 | — |
| Substudy 1 Parts 1a and 1b: Trough concentration (Ctrough) 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 Parts 1a and 1b: ORR in participants with B-cell malignancies | Up to approximately 3 years | ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator. |
| Substudy 2 Parts 1a and 1b: DOR | Up to approximately 3 years | DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first. |
| Substudy 2 Parts 1a and 1b: TTR | Up to approximately 3 years | TTR is defined as the time from treatment initiation to the first documented response. |
| 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 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 | Up to approximately 3 years | ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator. |
| Substudy 3 Parts 1a and 1b: DOR | Up to approximately 3 years | DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first. |
| Substudy 3 Parts 1a and 1b: TTR | Up to approximately 3 years | TTR is defined as the time from treatment initiation to the first documented response. |
| 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 | Up to approximately 3 years | ORR is defined as the percentage of participants with partial response (PR) or better as assessed by the investigator. |
| Substudy 4 Parts 1a and 1b: DOR | Up to approximately 3 years | DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first. |
| Substudy 4 Parts 1a and 1b: TTR | Up to approximately 3 years | TTR is defined as the time from treatment initiation to the first documented response. |
| 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 | — |
| Substudy 1 Parts 1a and 1b: Overall Response Rate (ORR) in participants with B-cell malignancies | Up to approximately 3 years | ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by investigator. |
| Substudy 1 Parts 1a and 1b: Duration of Response (DOR) | Up to approximately 3 years | DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first. |
| Substudy 1 Parts 1a and 1b: Time to Response (TTR) | Up to approximately 3 years | TTR is defined as the time from treatment initiation to first documented response. |
| 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 | — |
Countries
Australia, Brazil, China, Germany, Italy, New Zealand, Poland, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed