Long-term Extension Study of Zanubrutinib (BGB-3111) Regimens in Participants With B-cell Malignancies

An Open-label, Multi-center, Long-term Extension Study of Zanubrutinib (BGB-3111) Regimens in Patients With B-cell Malignancies

The purpose of this study is to evaluate the long-term safety of zanubrutinib regimens in participants with B-cell malignancies who participated in a BeiGene parent study for zanubrutinib.

Study Overview

• Status: Active, not recruiting
• Conditions: B-cell Malignancies
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Actual): 955
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2606
      • Paratus Clinical Research Woden
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • East Albury, New South Wales, Australia, 2640
      • Border Medical Oncology
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Icon Cancer Centre Wesley
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Greenslopes, Queensland, Australia, 4120
      • Brisbane Clinic For Lymphoma
    • Tugun, Queensland, Australia, 4224
      • John Flynn Private Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Bedford PK, South Australia, Australia, 5042
      • Flinders Medical Centre
    • Kurralta Park, South Australia, Australia, 5037
      • Icon Cancer Centre Kurralta Park
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital Melbourne
    • Frankston, Victoria, Australia, 3199
      • Peninsula Private Hospital
    • Geelong, Victoria, Australia, 3220
      • Barwon Health the Geelong Hospital
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital Malvern
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing Municipality, China, 100000
      • Peking University Third Hospital
    • Beijing, Beijing Municipality, China, 100044
      • Peking University Peoples Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
    • Quanzhou, Fujian, China, 362000
      • Quanzhou First Affliated Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Xuzhou, Jiangsu, China, 221000
      • The Affiliated Hospital of Xuzhou Medical University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China, 200092
      • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology and Hospital of Blood Disease
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
• Czechia
  • Brno, Czechia, 62500
    • Fakultni nemocnice Brno
  • Hradec Králové, Czechia, 50005
    • Fakultni nemocnice Hradec Kralove
  • Olomouc, Czechia, 77900
    • Fakultni Nemocnice Olomouc
  • Ostrava, Czechia, 708 00
    • Fakultni nemocnice Ostrava
  • Prague, Czechia, 10034
    • University Hospital Vinohrady Hematology Department
  • Prague, Czechia, 10000
    • Vseobecna fakultni nemocnice v Praze
• France
  • Bordeaux, France, 33076
    • Centre de Lutte Contre Le Cancer Institut Bergonie
  • La Roche-sur-Yon, France, 85925
    • Centre Hospitalier Departemental de Vendee
  • Le Mans, France, 72037
    • Centre Hospitalier Le Mans
  • Paris, France, 75010
    • Hopital Saint Louis
  • PierreBenite, France, 69495
    • Chu Hopital Lyon Sud
  • Tours, France, 37000
    • Chu Tours Hopital Bretonneau
• Germany
  • Sigmaringen, Germany, 72488
    • Srh Kliniken Landkreis Sigmaringen
• Greece
  • Athens, Greece, 11528
    • General Hospital of Athens Alexandra
• Italy
  • Bologna, Italy, 40138
    • Policlinico Sorsola Malpighi, Aou Di Bologna
  • Meldola, Italy, 47014
    • Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
  • Milan, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Modena, Italy, 41124
    • Universita Degli Studi Di Modena Azienda Ospedaliere Policlinco
  • Novara, Italy, 28100
    • AOU Maggiore della Carità
  • Pavia, Italy, 27100
    • Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
  • Ravenna, Italy, 48121
    • Unita Di Ematologia, Dipartimento Di Ematologia Ed Oncologia
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Terni, Italy, 05100
    • Azienda Ospedaliera S Maria Di Terni
  • Torino, Italy, 10126
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
  • Udine, Italy, 33100
    • Aou Santa Maria Della Misericordia Di Udine
• Japan
  • Aichi-ken
    • Toyohashi, Aichi-ken, Japan, 441-8570
      • Toyohashi Municipal Hospital
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
    • Sapporo, Hokkaido, Japan, 064-0804
      • Aiiku Hospital
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam Umc Amc
  • Nijmegen, Netherlands, 6525 GA
    • Albert Schweitzer Ziekenhuis
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Auckland, New Zealand, 2025
    • Aotearoa Clinical Trials
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Hamilton Waikato, New Zealand, 3204
    • Waikato Hospital
  • Takapuna, New Zealand, 0622
    • North Shore Hospital
  • Tauranga, New Zealand, 3112
    • Tauranga Hospital
  • Wellington, New Zealand, 6021
    • Wellington Regional Hospital (Ccdhb)
• Poland
  • Bialystok, Poland, 15748
    • Interhem Opieka Szpitalna
  • Brzozów, Poland, 36-200
    • Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki Nr Im Dr Jana Biziela
  • Chorzów, Poland, 41-500
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Gdask, Poland, 80-219
    • Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii
  • Krakow, Poland, 30-510
    • Malopolskie Centrum Medyczne Sc
  • Lodz, Poland, 93-510
    • Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
  • Skorzewo Poznan, Poland, 60-185
    • Centrum Medyczne Pratia Poznań
• South Korea
  • Busan Gwang'yeogsi
    • Busan, Busan Gwang'yeogsi, South Korea, 47392
      • Inje University Busan Paik Hospital
    • Busan, Busan Gwang'yeogsi, South Korea, 49201
      • Dong A University Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • National Cancer Center
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, South Korea, 03722
      • Severance Hospital Yonsei University Health System
    • Seoul, Seoul Teugbyeolsi, South Korea, 135-740
      • Samsung Medical Center Hematology Oncology
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 8036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall Dhebron
  • Barcelona, Spain, 08916
    • Ico Hug Trias I Pujol
  • Girona, Spain, 17007
    • Ico Girona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Toledo, Spain, 45004
    • Hospital Universitario de Toledo
• Sweden
  • Lund, Sweden, 221 85
    • Skanes Universitetssjukhus I Lund
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset Solna
• Turkey (Türkiye)
  • Tekirdağ, Turkey (Türkiye), 59100
    • Namik Kemal University
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Nhs Grampian Ppds
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Bournemouth, United Kingdom, BH7 7DW
    • The Royal Bournemouth and Christchurch Hospitals Nhs Foundation
  • Canterbury, United Kingdom, CT1 3NG
    • Kent and Canterbury Hospital
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Greater Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • Headington, United Kingdom, OX3 7LE
    • Churchill Hospital Oxford University Hospital Nhs Trust
  • Leeds, United Kingdom, LS9 7LP
    • St Jamess Institute of Oncology
  • London, United Kingdom, EC1A 7BE
    • Barts Health NHS Trust
  • London, United Kingdom, NW1 2PG
    • University College Hospital
  • Nottingham, United Kingdom, NG51PB
    • Nottingham University Hospitals NHS Trust
  • Plymouth, United Kingdom, PL6 8DH
    • Plymouth Hospitals NHS Trust
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • CARTI Cancer Center
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Rocky Mountain Cancer Centers Centennial
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists Fort Myers
    • St. Petersburg, Florida, United States, 33705
      • SCRI Florida Cancer Specialists North
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Forrest General Hospital Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • New York
    • Westbury, New York, United States, 11590
      • Clinical Research Alliance, Inc
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Hospital
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oncology Associates of Oregon Willamette Valley Cancer Center
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Scri Tennessee Oncology Chattanooga
    • Nashville, Tennessee, United States, 37205
      • Tennessee Oncology
  • Texas
    • Fort Worth, Texas, United States, 76104-2150
      • Texas Oncology Fort Worth Cancer Center
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78240
      • Texas Oncology San Antonio Medical Center Usor
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia, Inc
  • Washington
    • Seattle, Washington, United States, 98185
      • University of Washington Seattle Cancer Alliance
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

1. Currently participating or participated recently in a BeiGene parent study

2. Intent to continue or start zanubrutinib treatment after any of the following:

   1. At time of final analysis or study closure of the eligible BeiGene parent study
   2. At time of progressive disease (PD); and investigator, patient and medical monitor agree it is in the patient's best interest
   3. At an alternative timepoint for an alternative reason

3. Patient who is currently on zanubrutinib treatment:

   Does not meet any protocol-specified criteria for zanubrutinib hold or permanent discontinuation, and, in the opinion of the investigator, will continue to benefit from zanubrutinib treatment

4. Zanubrutinib-naive patient:

   Must meet the following criteria ≤ 15 days before first dose of study drug:

   1. Platelets ≥ 50,000/mm3
   2. Absolute neutrophil count ≥ 750/mm3
   3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal
   4. Serum total bilirubin ≤ 3 x upper limit of normal (not required for Gilbert Syndrome)
   5. QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤ 480 msec
   6. No known New York Heart Association (NYHA) Class III or IV congestive heart failure
   7. Creatinine clearance ≥ 30 mL/min
5. Female participants of childbearing potential and nonsterile males must be willing to use a highly effective method of birth control.

Key Exclusion Criteria:

1. Permanently discontinued from zanubrutinib treatment in the BeiGene parent study due to unacceptable toxicity, non-compliance with study procedures, or withdrawal of consent
2. Uncontrolled active systemic infection or recent infection requiring parenteral anti-microbial therapy
3. Life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of zanubrutinib, or put the study outcomes at undue risk
4. Concomitant chemotherapy, targeted therapy, radiation therapy, antibody-based therapies, or any prohibited concomitant therapy outlined in the protocol
5. Pregnant or lactating woman
6. Inability to comply with study procedures
7. Concurrent participation in another therapeutic clinical study
8. History of progressive disease (PD) while receiving a BTK inhibitor (excluding zanubrutinib)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib (BGB-3111); All participants to receive open-label zanubrutinib	Drug: Zanubrutinib; Participants will receive zanubrutinib at a dose of 160 mg twice daily (for a total daily dose of 320 mg), or the last dose level received in the BeiGene parent study.; Other Names: BGB-3111
Experimental: Zanubrutinib in combination with Tislelizumab; Participants to receive the combination as in the parent study (Australia Only)	Drug: Zanubrutinib; Participants will receive zanubrutinib at a dose of 160 mg twice daily (for a total daily dose of 320 mg), or the last dose level received in the BeiGene parent study.; Other Names: BGB-3111; Drug: Tislelizumab; Patients in Australia who participated in a parent study that involved combination therapy of zanubrutinib and tislelizumab will receive tislelizumab at a dose of 200mg every 3 weeks..; Other Names: BGB-A317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)	Safety as assessed by incidence of all treatment-emergent adverse events (TEAEs) and serious AEs (SAEs)	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) per investigator assessment	Time from the starting date of zanubrutinib in the eligible BeiGene study to the date of first documentation of disease progression or death, whichever occurs first	Up to 5 years
Duration of Response (DOR) per investigator assessment	Time from the date that response criteria are first met after the start of zanubrutinib in the eligible BeiGene study to the date that progressive disease (PD) is objectively documented or death, whichever occurs first	Up to 5 years
Overall Survival (OS)	Time from the starting date of zanubrutinib in the eligible BeiGene study to the date of death due to any reason	Up to 5 years

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Publications and helpful links

General Publications

• Garcia-Sanz R, Owen RG, Jurczak W, Dimopoulos MA, McCarthy H, Cull G, Opat SS, Castillo JJ, Kersten MJ, Wahlin BE, Grosicki S, Prathikanti R, Tian T, Allewelt H, Cohen A, Tam CS. Outcomes following transition from ibrutinib to zanubrutinib in patients with Waldenstrom macroglobulinemia from ASPEN. Blood Adv. 2025 Sep 9:bloodadvances.2024015596. doi: 10.1182/bloodadvances.2024015596. Online ahead of print.
• Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2020
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Estimated): October 21, 2025
• Last Update Submitted That Met QC Criteria: October 20, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Zanubrutinib; Bruton's tyrosine kinase (BTK) inhibitor; long-term extension
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib; tislelizumab
• Other Study ID Numbers: BGB-3111-LTE1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No