Clinical trial • Phase I/II • Oncology

BGB-16673 for Relapsed or Refractory B-cell malignancies | Diffuse large B-cell lymphoma | Follicular lymphoma | Chronic lymphocytic leukemia | Mantle cell lymphoma | Marginal zone lymphoma | Waldenström macroglobulinaemia | Richter's syndrome

Phase I/II trial of BGB-16673 for Relapsed or Refractory B-cell malignancies | Diffuse large B-cell lymphoma | Follicular lymphoma | Chronic lymphocytic l…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Relapsed or Refractory B-cell malignancies | Diffuse large B-cell lymphoma | Follicular lymphoma | Chronic lymphocytic leukemia | Mantle cell lymphoma | Marginal zone lymphoma | Waldenström macroglobulinaemia | Richter's syndrome
Trial Stage
Phase I/II
Drug Modality
Small molecule|Monoclonal antibody|Bispecific antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
29-05-2025
First CTIS Authorization Date
23-09-2025

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial across 15 sites in Germany, Italy, Poland.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, dose-escalation elements are included to identify recommended dose(s) for expansion (RDFE[s]) and assess dose-limiting toxicities (Part 1a); master protocol with substudy-specific escalation/expansion elements
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
271

Eligibility

Recruits 271 Vulnerable population selected. All participants must be capable of giving written informed consent and must sign an informed consent form (ICF). Study-specific and substudy-specific subject information sheets and ICFs are provided; ICF documentation includes versions in German, Italian and Polish. Paediatric subjects are excluded, so assent is not applicable..

Pregnancy Exclusion
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, or 90 days after the last dose of sonrotoclax, 3 months after the last dose of mosunetuzumab or tocilizumab, 18 months after pretreatment with obinutuzumab, 2 months after the last dose of glofitamab. A negative urine or serum pregnancy test result must be provided 10-14 days before the first dose of study treatment
Vulnerable Population
Vulnerable population selected. All participants must be capable of giving written informed consent and must sign an informed consent form (ICF). Study-specific and substudy-specific subject information sheets and ICFs are provided; ICF documentation includes versions in German, Italian and Polish. Paediatric subjects are excluded, so assent is not applicable.

Inclusion criteria

  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Adequate renal function as indicated by eGFR of ≥ 30 mL/min (Sub-study 2)"}
  • {"criterion_text":"- Confirmed diagnosis of a R/R B-cell malignancy"}
  • {"criterion_text":"- Protocol-defined measurable disease"}
  • {"criterion_text":"- Stable Eastern Cooperative Oncology Group Performance Status of 0 to 1"}
  • {"criterion_text":"- Adequate organ function"}
  • {"criterion_text":"- 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, or 90 days after the last dose of sonrotoclax, 3 months after the last dose of mosunetuzumab or tocilizumab, 18 months after pretreatment with obinutuzumab, 2 months after the last dose of glofitamab. A negative urine or serum pregnancy test result must be provided 10-14 days before the first dose of study treatment"}
  • {"criterion_text":"- 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, 90 days after the last dose of sonrotoclax, 3 months after the last dose of mosunetuzumab or tocilizumab, 18 months after pretreatment with obinutuzumab, 2 months after the last dose of glofitamab"}
  • {"criterion_text":"- Adequate renal function as indicated by estimated glomerular filtration rate (eGFR) of ≥ 50 mL/min (Sub-studies 1, 3 and 4)"}
  • {"criterion_text":"- Bruton tyrosine kinase (BTK) inhibitor-naive, or previously received treatment with a covalent BTK inhibitor and discontinued for reasons other than clinical progression (Sub-study 2)"}

Exclusion criteria

  • {"criterion_text":"- Treatment-naive B-cell malignancies, except for patients in Substudy 1 Cohorts 5 and 6."}
  • {"criterion_text":"- Prior exposure to a CD20 x CD3 T-cell engager antibody treatment (Sub-studies 3 and 4)"}
  • {"criterion_text":"- All participants with a prior allogeneic stem cell transplant (Sub-studies 3 and 4)"}
  • {"criterion_text":"- Unable to comply with the requirements of the protocol"}
  • {"criterion_text":"- Active leptomeningeal disease or uncontrolled, untreated brain metastasis"}
  • {"criterion_text":"- Any malignancy ≤ 2 years before first dose of study treatment except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively"}
  • {"criterion_text":"- Autologous stem cell transplant ≤ 3 months prior to screening or chimeric antigen T-cell therapy ≤ 3 months prior to screening"}
  • {"criterion_text":"- 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 (Sub-studies 1 and 2)"}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- 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) (Sub-study 1)"}
  • {"criterion_text":"- Participants who discontinued prior zanubrutinib treatment due to intolerance (Sub-study 2)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Number of patients with dose-limiting toxicities (Part 1a)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of patients with treatment-emergent adverse events (Part 1a, part 1b)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of patients with treatment-related adverse events (Part 1a, part 1b)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of patients with serious adverse events (Part 1a, part 1b)","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Overall response rate (ORR) as assessed by the investigator (Part 1a, part 1b)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Duration of response (DOR) (Part 1a, part 1b)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Time-to-response (TTR) (Part 1a, part 1b)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Derived PK parameters of BGB-16673 (Part 1a)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Plasma concentration data (Part 1a, part 1b)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Number of patients with complete response/complete response with incomplete count recovery (CR/CRi) who achieve uMRD status with < 10^(-4) sensitivity in peripheral blood and/or bone marrow (Part 1b, sub-study 1 only)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Derived PK parameters of sonrotoclax (Part 1a, sub-study 1 only)","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
271
Recruitment Window Months
43
Consent Approach
Participants must sign an informed consent form (ICF) and be capable of giving written informed consent. Subject information sheets and ICFs are provided for the main study and substudy-specific ICFs; documentation includes versions in German, Italian and Polish. No paediatric assent procedures are applicable because paediatric subjects are excluded.

Geography

Total Number Of Sites
15
Total Number Of Participants
99

Germany

Earliest CTIS Part Ii Submission Date
17-08-2025
Latest Decision Or Authorization Date
23-04-2026
Processing Time Days
249
Number Of Sites
5
Number Of Participants
30

Sites

Site Name
Technische Universitaet Dresden
Department Name
Medizinische Klinik und Poliklinik I
Principal Investigator Name
Frank Kroschinsky
Principal Investigator Email
xxx@ukdd.de
Contact Person Name
Frank Kroschinsky
Contact Person Email
xxx@ukdd.de
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Comprehensive Cancer Center Ulm
Principal Investigator Name
Eugen Tausch
Principal Investigator Email
xxx@uniklinik-ulm.de
Contact Person Name
Eugen Tausch
Contact Person Email
xxx@uniklinik-ulm.de
Site Name
Universitaetsklinikum Jena KöR
Department Name
Hämatologie und internistische Onkologie
Principal Investigator Name
Ulf Schnetzke
Principal Investigator Email
xxx@med.uni-jena.de
Contact Person Name
Ulf Schnetzke
Contact Person Email
xxx@med.uni-jena.de
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Medical Department II
Principal Investigator Name
Christiane Pott
Principal Investigator Email
xxx@med2.uni-kiel.de
Contact Person Name
Christiane Pott
Contact Person Email
xxx@med2.uni-kiel.de
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Medizinische Klinik, Innere Medizin II
Principal Investigator Name
Stefan Wirths
Principal Investigator Email
xxx@med.uni-tuebingen.de
Contact Person Name
Stefan Wirths
Contact Person Email
xxx@med.uni-tuebingen.de

Italy

Earliest CTIS Part Ii Submission Date
25-07-2025
Latest Decision Or Authorization Date
29-04-2026
Processing Time Days
277
Number Of Sites
5
Number Of Participants
33

Sites

Site Name
Humanitas Mirasole S.p.A.
Department Name
Experimental Therapeutics Unit and Lymphoma Unit
Principal Investigator Name
Carmelo Carlo-Stella
Principal Investigator Email
carmelo.carlostella@hunimed.eu
Contact Person Name
Carmelo Carlo-Stella
Contact Person Email
carmelo.carlostella@hunimed.eu
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
U.O.C. Ematologia
Principal Investigator Name
Pier Luigi Zinzani
Principal Investigator Email
pierluigi.zinzani@unibo.it
Contact Person Name
Pier Luigi Zinzani
Contact Person Email
pierluigi.zinzani@unibo.it
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
S.C. Ematologia Oncologica e Trapianto di Cellule Staminali
Principal Investigator Name
Antonio Pinto
Principal Investigator Email
a.pinto@istitutotumori.na.it
Contact Person Name
Antonio Pinto
Contact Person Email
a.pinto@istitutotumori.na.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
S.C. Ematologia e UTMO
Principal Investigator Name
Anna Maria Frustaci
Principal Investigator Email
annamaria.frustaci@ospedaleniguarda.it
Contact Person Name
Anna Maria Frustaci
Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Department Name
Hematology Unit
Principal Investigator Name
Carlo Visco
Principal Investigator Email
carlo.visco@univr.it
Contact Person Name
Carlo Visco
Contact Person Email
carlo.visco@univr.it

Poland

Earliest CTIS Part Ii Submission Date
02-09-2025
Latest Decision Or Authorization Date
05-05-2026
Processing Time Days
245
Number Of Sites
5
Number Of Participants
36

Sites

Site Name
Szpital Kliniczny Ministerstwa Spraw Wewnetrznych I Administracji Z Warminsko-Mazurskim Centrum Onkologii W Olsztynie
Department Name
Oddział Kliniczny Hematologii i Chorób Wewnętrznych z Ośrodkiem Transplantacji Szpiku
Principal Investigator Name
Janusz Hałka
Principal Investigator Email
janusz.halka@poliklinika.net
Contact Person Name
Janusz Hałka
Contact Person Email
janusz.halka@poliklinika.net
Site Name
Uniwersytecki Szpital Kliniczny Nr 1 W Lublinie
Department Name
Klinika Hematoonkologii i Transplantacji Szpiku
Principal Investigator Name
Marek Hus
Principal Investigator Email
hematoonkologia@usk1.lublin.pl
Contact Person Name
Marek Hus
Contact Person Email
hematoonkologia@usk1.lublin.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworów Układu Chłonnego
Principal Investigator Name
Ewa Paszkiewicz-Kozik
Principal Investigator Email
ewa.paszkiewicz-kozik@nio.gov.pl
Contact Person Name
Ewa Paszkiewicz-Kozik
Site Name
Szpital Wojewodzki W Opolu Sp. z o.o.
Department Name
Oddział Kliniczny Hematologii, Onkologii Hematologicznej i Chorób Wewnętrznych
Principal Investigator Name
Dariusz Woszczyk
Principal Investigator Email
xx@szpital.opole.pl
Contact Person Name
Dariusz Woszczyk
Contact Person Email
xx@szpital.opole.pl
Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Hematologii i Transplantologii
Principal Investigator Name
Michał Taszner
Principal Investigator Email
mtaszner@uck.gda.pl
Contact Person Name
Michał Taszner
Contact Person Email
mtaszner@uck.gda.pl

Sponsor

Primary sponsor

Full Name
BeOne Medicines AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
WCG Clinical Inc.
Responsibilities
Distribution of Clinical Safety Reports
Name
4g Clinical LLC
Responsibilities
code 3
Name
Iqvia Laboratories Limited
Responsibilities
code 4
Name
Medidata Solutions Inc.
Responsibilities
code 4

Third parties

  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"code 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"China","full_name":"Wuxi Biologics (Shanghai) Co. Ltd.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"code 4","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Poland","full_name":"Komtur Polska Sp. z o.o.","duties_or_roles":"Local supply of rescue medication","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 4","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Distribution of Clinical Safety Reports","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ledger Run Inc.","duties_or_roles":"Site payments","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BGB-16673
Active Substance
BGB-16673
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Investigational Product Name
BGB-11417
Active Substance
N-[4-({[(1R,4R)-4-HYDROXY-4-METHYLCYCLOHEXYL]METHYL}AMINO)-3- NITROBENZENE-1-SULFONYL]-4-(2-{(2S)-2-[2-(PROPAN-2-YL)PHENYL]PYRROLIDIN1-YL}-7-AZASPIRO[3.5]NONAN-7-YL)-2-[(1H-PYRROLO[2,3-B]PYRIDIN-5- YL)OXY]BENZAMIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Investigational Product Name
Zanubrutinib
Active Substance
ZANUBRUTINIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Investigational Product Name
Mosunetuzumab
Active Substance
MOSUNETUZUMAB
Modality
Bispecific antibody
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Investigational Product Name
Columvi (glofitamab)
Active Substance
GLOFITAMAB
Modality
Bispecific antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Marketing authorisation number EU/1/23/1742/002
Orphan Designation
Yes
Investigational Product Name
Gazyvaro (obinutuzumab)
Active Substance
OBINUTUZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Marketing authorisation number EU/1/14/937/001
Orphan Designation
Yes
Combination Treatment
Yes

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