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
- Phase
- Phase 1
- Intervention
- Glofitamab
- Conditions
- B-cell Malignancy
- Sponsor
- BeOne Medicines
- Enrollment
- 80
- Locations
- 75
- Primary Endpoint
- Substudy 1 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
- Status
- Recruiting
- Last Updated
- 17 days ago
Overview
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.
Investigators
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 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:
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:
Arms & Interventions
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.
Intervention: Glofitamab
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.
Intervention: Obinutuzumab
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.
Intervention: BGB-16673
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.
Intervention: BGB-16673
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.
Intervention: Zanubrutinib
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.
Intervention: BGB-16673
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.
Intervention: Mosunetuzumab
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.
Intervention: Mosunetuzumab
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.
Intervention: Zanubrutinib
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.
Intervention: BGB-16673
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.
Intervention: BGB-16673
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.
Intervention: BGB-16673
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.
Intervention: Sonrotoclax
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.
Intervention: BGB-16673
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.
Intervention: Sonrotoclax
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.
Intervention: BGB-16673
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.
Intervention: Obinutuzumab
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.
Intervention: Glofitamab
Outcomes
Primary Outcomes
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 Outcomes
- Substudy 1 Parts 1a and 1b: Overall Response Rate (ORR) in participants with B-cell malignancies(Up to approximately 3 years)
- Substudy 1 Parts 1a and 1b: Duration of Response (DOR)(Up to approximately 3 years)
- Substudy 1 Parts 1a and 1b: Time to Response (TTR)(Up to approximately 3 years)
- 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 2 Parts 1a and 1b: ORR in participants with B-cell malignancies(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 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 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 3 Parts 1a and 1b: ORR in participants with B-cell malignancies(Up to approximately 3 years)
- Substudy 2 Parts 1a and 1b: DOR(Up to approximately 3 years)
- Substudy 2 Parts 1a and 1b: TTR(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 3 Parts 1a and 1b: DOR(Up to approximately 3 years)
- Substudy 3 Parts 1a and 1b: TTR(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(Up to approximately 3 years)
- Substudy 4 Parts 1a and 1b: DOR(Up to approximately 3 years)
- Substudy 4 Parts 1a and 1b: TTR(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)