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

Phase 2RecruitingNCT06634589

BeOne Medicines80 enrolled

Overview

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.

This new study will check how safe and helpful a potential anticancer drug called tacabrutideg 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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

B-cell Malignancy Relapsed Cancer Refractory Cancer

Interventions

TacabrutidegDRUG

Administered orally

SonrotoclaxDRUG

Administered orally

ZanubrutinibDRUG

Administered orally

MosunetuzumabDRUG

Administered subcutaneously

GlofitamabDRUG

Administered intravenously

ObinutuzumabDRUG

Administered intravenously

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (49)

Mayo Clinic Phoenix

Phoenix, Arizona, United States

RECRUITING

University of Southern California Norris Comprehensive

Los Angeles, California, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

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

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by investigator.

Time frame: Up to approximately 3 years

Substudy 1 Parts 1a and 1b: Duration of Response (DOR)

DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.

Time frame: Up to approximately 3 years

Substudy 1 Parts 1a and 1b: Time to Response (TTR)

TTR is defined as the time from treatment initiation to first documented response.

Time frame: Up to approximately 3 years

Substudy 1 Part 1a: Area under the plasma concentration-time curve (AUC) of tacabrutideg and sonrotoclax

Time frame: From Week 1 to Week 17

Substudy 1 Part 1a: Maximum observed concentration (Cmax) of tacabrutideg and sonrotoclax

Time frame: From Week 1 to Week 17

Substudy 1 Part 1a: Time to maximum concentration (Tmax) of tacabrutideg and sonrotoclax

Time frame: From Week 1 to Week 17

Substudy 1 Part 1a: Terminal half-life (t1/2) of tacabrutideg and sonrotoclax

Time frame: From Week 1 to Week 17

Substudy 1 Parts 1a and 1b: Trough concentration (Ctrough) of tacabrutideg and sonrotoclax

Time frame: 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)

Time frame: Up to approximately 3 years

Central Contacts

Study Director

CONTACT

1.877.828.5568 clinicaltrials@beonemed.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

The University of Kansas Cancer Center

Westwood, Kansas, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

RECRUITING

Icahn School of Medicine At Mount Sinai

New York, New York, United States

RECRUITING

Columbia University Medical Center

New York, New York, United States

RECRUITING

Weill Cornell Medical College Newyork Presbyterian Hospital

New York, New York, United States

RECRUITING

...and 39 more locations

Substudy 2 Parts 1a and 1b: ORR in participants with B-cell malignancies

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator.

Time frame: Up to approximately 3 years

Substudy 2 Parts 1a and 1b: DOR

DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.

Time frame: Up to approximately 3 years

Substudy 2 Parts 1a and 1b: TTR

TTR is defined as the time from treatment initiation to the first documented response.

Time frame: Up to approximately 3 years

Substudy 2 Part 1a: Area under the plasma concentration-time curve (AUC) of tacabrutideg and zanubrutinib

Time frame: From Week 1 to Week 17

Substudy 2 Part 1a: Maximum observed concentration (Cmax) of tacabrutideg and zanubrutinib

Time frame: From Week 1 to Week 17

Substudy 2 Part 1a: Time to maximum concentration (Tmax) of tacabrutideg and zanubrutinib

Time frame: From Week 1 to Week 17

Substudy 2 Part 1a: Terminal half-life (t1/2) of tacabrutideg and zanubrutinib

Time frame: From Week 1 to Week 17

Substudy 2 Parts 1a and 1b: Trough concentration (Ctrough) of tacabrutideg and zanubrutinib

Time frame: 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

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator.

Time frame: Up to approximately 3 years

Substudy 3 Parts 1a and 1b: DOR

DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.

Time frame: Up to approximately 3 years

Substudy 3 Parts 1a and 1b: TTR

TTR is defined as the time from treatment initiation to the first documented response.

Time frame: Up to approximately 3 years

Substudy 3 Part 1a: Area under the plasma concentration-time curve (AUC) of tacabrutideg and mosunetuzumab

Time frame: From Week 1 to Week 12

Substudy 3 Part 1a: Maximum observed concentration (Cmax) of tacabrutideg and mosunetuzumab

Time frame: From Week 1 to Week 12

Substudy 3 Part 1a: Time to maximum concentration (Tmax) of tacabrutideg and mosunetuzumab

Time frame: From Week 1 to Week 12

Substudy 3 Part 1a: Terminal half-life (t1/2) of tacabrutideg and mosunetuzumab

Time frame: From Week 1 to Week 12

Substudy 3 Parts 1a and 1b: Trough concentration (Ctrough) of tacabrutideg and mosunetuzumab

Time frame: From Week 1 to Week 36

Substudy 4 Parts 1a and 1b: ORR in participants with B-cell malignancies

ORR is defined as the percentage of participants with partial response (PR) or better as assessed by the investigator.

Time frame: Up to approximately 3 years

Substudy 4 Parts 1a and 1b: DOR

DOR is defined as the time from the first documented response to documented disease progression or death, whichever occurs first.

Time frame: Up to approximately 3 years

Substudy 4 Parts 1a and 1b: TTR

TTR is defined as the time from treatment initiation to the first documented response.

Time frame: Up to approximately 3 years

Substudy 4 Part 1a: Area under the plasma concentration-time curve (AUC) of tacabrutideg

Time frame: From Week 1 to Week 10

Substudy 4 Part 1a: Maximum observed concentration (Cmax) of tacabrutideg

Time frame: From Week 1 to Week 10

Substudy 4 Part 1a: Time to maximum concentration (Tmax) of tacabrutideg

Time frame: From Week 1 to Week 10

Substudy 4 Part 1a: Terminal half-life (t1/2) of tacabrutideg

Time frame: From Week 1 to Week 10

Substudy 4 Parts 1a and 1b: Trough concentration (Ctrough) of tacabrutideg

Time frame: From Week 1 to Week 10