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

BeiGene

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Relapsed Cancer; Refractory Cancer; B-cell Lymphoma; B-cell Malignancy

Treatments: Drug: Mosunetuzumab; Drug: Glofitamab; Drug: Sonrotoclax; Drug: Obinutuzumab; Drug: Zanubrutinib; Drug: BGB-16673

Study type: Interventional

Funder types: Industry

Identifiers

NCT06634589

BGB-16673-104

2024-516234-35-00 (EU Trial (CTIS) Number)

CTR20244676 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 8 patient groups

Substudy 1 Part 1a: Dose Escalation

Experimental group

Description:

Sequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies.

Treatment:

Drug: BGB-16673

Drug: Sonrotoclax

Substudy 1 Part 1b: Safety Expansion

Experimental group

Description:

Cohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies.

Treatment:

Drug: BGB-16673

Drug: Sonrotoclax

Substudy 2 Part 1a: Dose Escalation

Experimental group

Description:

Sequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies.

Treatment:

Drug: BGB-16673

Drug: Zanubrutinib

Substudy 2 Part 1b: Safety Expansion

Experimental group

Description:

Cohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies.

Treatment:

Drug: BGB-16673

Drug: Zanubrutinib

Substudy 3 Part 1a: Dose Escalation

Experimental group

Description:

Sequential cohorts of increasing dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies.

Treatment:

Drug: BGB-16673

Drug: Mosunetuzumab

Substudy 3 Part 1b: Safety Expansion

Experimental group

Description:

Cohorts of select dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies.

Treatment:

Drug: BGB-16673

Drug: Mosunetuzumab

Substudy 4 Part 1a: Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: BGB-16673

Drug: Obinutuzumab

Drug: Glofitamab

Substudy 4 Part 1b: Safety Expansion

Experimental group

Description:

Cohorts of select dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies.

Treatment:

Drug: BGB-16673

Drug: Obinutuzumab

Drug: Glofitamab