Clinical trial NCT06634589: A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Malignancy
Relapsed Cancer
Refractory Cancer
B-cell Lymphoma
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
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-10-10
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Substudy 1 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
measure: Substudy 1 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
measure: Substudy 2 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
measure: Substudy 2 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
measure: Substudy 3 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
measure: Substudy 3 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years]
measure: Substudy 4 Part 1a: Number of participants with dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
measure: Substudy 4 Part 1b: Number of participants with treatment-emergent adverse events, treatment-related adverse events, and serious adverse events
timeFrame: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 2 years
Secondary outcomes:
measure: Substudy 1 Parts 1a and 1b: Overall Response Rate (ORR) in participants with B-cell malignancies
timeFrame: Up to approximately 3 years
measure: Substudy 1 Parts 1a and 1b: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: Substudy 1 Parts 1a and 1b: Time to Response (TTR)
timeFrame: Up to approximately 3 years
measure: Substudy 1 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and sonrotoclax
timeFrame: From Week 1 to Week 17
measure: Substudy 1 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and sonrotoclax
timeFrame: From Week 1 to Week 17
measure: Substudy 1 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and sonrotoclax
timeFrame: From Week 1 to Week 17
measure: Substudy 1 Part 1a: Terminal half-life (t1/2) of BGB-16673 and sonrotoclax
timeFrame: From Week 1 to Week 17
measure: Substudy 1 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and sonrotoclax
timeFrame: From Week 1 to Week 17
measure: 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)
timeFrame: Up to approximately 3 years
measure: Substudy 2 Parts 1a and 1b: ORR in participants with B-cell malignancies
timeFrame: Up to approximately 3 years
measure: Substudy 2 Parts 1a and 1b: DOR
timeFrame: Up to approximately 3 years
measure: Substudy 2 Parts 1a and 1b: TTR
timeFrame: Up to approximately 3 years
measure: Substudy 2 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and zanubrutinib
timeFrame: From Week 1 to Week 17
measure: Substudy 2 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and zanubrutinib
timeFrame: From Week 1 to Week 17
measure: Substudy 2 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and zanubrutinib
timeFrame: From Week 1 to Week 17
measure: Substudy 2 Part 1a: Terminal half-life (t1/2) of BGB-16673 and zanubrutinib
timeFrame: From Week 1 to Week 17
measure: Substudy 2 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and zanubrutinib
timeFrame: From Week 1 to Week 17 for Part 1a; From Week 1 to Week 5 for Part 1b
measure: Substudy 3 Parts 1a and 1b: ORR in participants with B-cell malignancies
timeFrame: Up to approximately 3 years
measure: Substudy 3 Parts 1a and 1b: DOR
timeFrame: Up to approximately 3 years
measure: Substudy 3 Parts 1a and 1b: TTR
timeFrame: Up to approximately 3 years
measure: Substudy 3 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673 and mosunetuzumab
timeFrame: From Week 1 to Week 12
measure: Substudy 3 Part 1a: Maximum observed concentration (Cmax) of BGB-16673 and mosunetuzumab
timeFrame: From Week 1 to Week 12
measure: Substudy 3 Part 1a: Time to maximum concentration (Tmax) of BGB-16673 and mosunetuzumab
timeFrame: From Week 1 to Week 12
measure: Substudy 3 Part 1a: Terminal half-life (t1/2) of BGB-16673 and mosunetuzumab
timeFrame: From Week 1 to Week 12
measure: Substudy 3 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673 and mosunetuzumab
timeFrame: From Week 1 to Week 36
measure: Substudy 4 Parts 1a and 1b: ORR in participants with B-cell malignancies
timeFrame: Up to approximately 3 years
measure: Substudy 4 Parts 1a and 1b: DOR
timeFrame: Up to approximately 3 years
measure: Substudy 4 Parts 1a and 1b: TTR
timeFrame: Up to approximately 3 years
measure: Substudy 4 Part 1a: Area under the plasma concentration-time curve (AUC) of BGB-16673
timeFrame: From Week 1 to Week 10
measure: Substudy 4 Part 1a: Maximum observed concentration (Cmax) of BGB-16673
timeFrame: From Week 1 to Week 10
measure: Substudy 4 Part 1a: Time to maximum concentration (Tmax) of BGB-16673
timeFrame: From Week 1 to Week 10
measure: Substudy 4 Part 1a: Terminal half-life (t1/2) of BGB-16673
timeFrame: From Week 1 to Week 10
measure: Substudy 4 Parts 1a and 1b: Trough concentration (Ctrough) of BGB-16673
timeFrame: From Week 1 to Week 10
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern Californianorris Comprehensive
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: New York
country: United States
facility: Icahn School of Medicine At Mount Sinai
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College Newyork Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Mskcc
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Md Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Cancer Care Centre
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Brasilia
country: Brazil
facility: Hospital Sirio Libanes Brasilia
city: Salvador
country: Brazil
facility: Ensino E Terapia de Inovacao Clinica Amo Etica
city: Sao Jose Do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicinechengzhan
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
city: Jena
country: Germany
facility: Universitatsklinikum Jena Klinik Fur Innere Medizin Ii
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig Holstein, Campus Kiel
city: Tubingen
country: Germany
facility: Medizinische Universitaetsklinik
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G Pascale
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Centroricerche Cliniche Di Verona Srl
city: Auckland
country: New Zealand
facility: North Shore Hospital
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Gdask
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr W Lublinie
city: Olsztyn
country: Poland
facility: Szpital Kliniczny Mswia Z Warmisko Mazurskim Centrum Onkologii
city: Opole
country: Poland
facility: Szpital Wojewodzki W Opolu Sp Z Oo Oddzia Hematologii I Onkologii Hematologicznej
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Hematology Unit
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: