BTK Inhibitor BGB-3111 in Chinese Participants With Diffuse Large B-Cell Lymphoma (Non-GCB) and Indolent Lymphoma (FL and MZL)

NCT03520920 | Completed Phase 2 Results DMC

• 2 other identifiers: BGB-3111-213CTR20170965
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

Brief Summary

This was a multicenter, open-label, phase 2 study to evaluate efficacy, safety, and tolerability of BGB-3111 (zanubrutinib) 160 milligrams (mg) twice daily (BID) in combination with rituximab in Chinese participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (non-GCB \[non-germinal center B-cell-like\] subtype) and R/R indolent lymphoma (follicular lymphoma \[FL\] and marginal zone lymphoma \[MZL\]).

Conditions

Marginal Zone Lymphoma; Follicular Lymphoma; Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) As Measured By The Investigator

  The percentage of participants whose best overall response met partial response (PR) or complete response (CR) criteria among all participants. The 95% confidence interval (CI) was calculated with the Clopper-Pearson method.

  Up to approximately 2.5 years

Secondary Outcomes (10)

• Duration Of Response (DOR) As Determined By Investigator

  Up to approximately 2.5 years

• DOR: Event-free Rate

  Up to approximately 2.5 years

• Progression-free Survival (PFS) As Determined By Investigator

  Up to approximately 2.5 years

• PFS: Event-free Rate

  Up to approximately 2.5 years

• Overall Survival (OS)

  Up to approximately 2.5 years

Study Arms (2)

R/R Non-GCB DLBCL

EXPERIMENTAL

Participants with non-GCB DLBCL received zanubrutinib plus rituximab for up to progressive disease or intolerance.

Drug: Zanubrutinib; Drug: Rituximab

R/R FL or MZL

EXPERIMENTAL

Participants with R/R FL or MZL received zanubrutinib plus rituximab for up to progressive disease or intolerance.

Drug: Zanubrutinib; Drug: Rituximab

Interventions

Zanubrutinib DRUG

Administered zanubrutinib 160 mg orally (PO) BID continuously

Also known as: BGB-3111

R/R FL or MZL; R/R Non-GCB DLBCL

Rituximab DRUG

Administered rituximab 375 mg/m\^2 intravenously on Cycle 1 Days 1, 8, 15, 22, and on Day 1 of Cycles 4, 6, 8, 10. Each cycle was 28 days long.

R/R FL or MZL; R/R Non-GCB DLBCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ Age 18 years at time of signing of informed consent.
• Measurable disease by computed tomography (CT) or positron emission tomography/CT or magnetic resonance imaging, defined as ≥1 nodal lesion that was \>1.5 centimeters (cm) in the longest diameter, or ≥1 extra-nodal lesion (for example, hepatic nodules) that was \>1 cm in the longest diameter.
• Availability of archival or fresh tumor tissue sample from an evaluable core or excisional biopsy.
• Participants meet the following criteria:
• Cohort 1: R/R non-GCB DLBCL i. Histologically confirmed non-GCB DLBCL per Hans criteria with non-transformed disease; additional methodologies for confirming non-GCB DLBCL may have been considered in consultation with the medical monitor. ii. Relapsed disease (disease progression after most recent therapy for DLBCL occurring more than 6 months after the completion of last therapy) or refractory disease (failure to achieve complete response \[CR\] or partial response \[PR\] to therapy for non-GCB DLBCL or disease progression within 6 months after completion of the most recent therapy for non-GCB DLBCL). iii. Must have received at least one standard anthracycline ± rituximab-based treatment (for example, rituximab plus cyclophosphamide, doxorubicin \[or epirubicin, hydroxydaunorubicin, or similar\], vincristine, and prednisone) or cyclophosphamide, vincristine, and prednisone +/- rituximab for DLBCL.
• Cohort 2: R/R FL or R/R MZL i. Histologically confirmed CD20+ FL (Grade 1, 2, or 3a) or MZL. ii. Relapsed disease (disease progression after most recent therapy for FL or MZL occurring more than 6 months after the completion of last therapy) or refractory disease (failure to achieve complete response (CR) or partial response (PR) to most recent therapy for FL or MZL, or disease progression within 6 months after completion of the most recent therapy for FL or MZL).
• Laboratory parameters as specified below:
• Hematologic: Platelet count ≥75 x 10\^9/liter (L) independent of growth factor or transfusion within 7 days of study entry; absolute neutrophil count (ANC) ≥1 x 10\^9/L independent of growth factor within 7 days of study entry, hemoglobin \>8 grams/deciliter within 7 days of study entry.
• Hepatic: Total bilirubin ≤ 2x upper limit of normal (ULN) unless documented Gilbert's syndrome; aspartate aminotransferase/serum glutamic-oxaloacetic transaminase and alanine transaminase/serum glutamic-pyruvic transaminase ≤3x ULN.
• Renal: Creatinine clearance ≥30 milliliters/minute (as estimated by the Cockcroft-Gault equation based on ideal body weight or as measured by nuclear medicine scan or 24-hour urine collection).
• International normalized ratio and activated partial thromboplastin time ≤1.5x ULN. Participants with anti-phospholipid syndrome, acquired von Willebrand disease, factor inhibitors or on vitamin K antagonist may have been enrolled after discussion with the Medical Monitor.
• Left ventricular ejection fraction ≥50%.
• Life expectancy ≥6 months.
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
• Female participants of childbearing potential must have practiced highly effective methods of contraception initiated prior to first dose of study drug, for the duration of the study, and for ≥90 days after the last dose of zanubrutinib, or 12 months after the last dose of rituximab, whichever is longer.

You may not qualify if:

• Known central nervous system lymphoma or leukemia.
• Histological confirmed gastric mucosa-associated lymphoid tissue type MZL.
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
• Clinically significant cardiovascular disease.
• History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
• Severe or debilitating pulmonary disease.
• Hypersensitivity reaction to zanubrutinib or rituximab or any of the other ingredients of the study drugs.
• Prior Bruton tyrosine kinase inhibitor treatment.
• Required ongoing treatment with a strong cytochrome P450 protein inhibitor or inducer.
• Vaccination with a live vaccine within 28 days of the first dose of study drug.
• Hematopoietic stem cell transplantation within 6 months of first dose of study drug.
• Receipt of the following treatment prior to first dose of study drug:
• Corticosteroids at doses \>20 mg/day prednisone equivalent or steroids given with anti-neoplastic intent within 7 days prior to first dose of study drug.
• Chemotherapy or radiotherapy within 4 weeks.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (4)

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

Location

Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200092, China

Location

Related Publications (1)

• Qingyuan Zhang, Rong Tao, Zhenyu Li, et al. Zanubrutinib (BGB-3111) in combination with rituximab in patients with relapsed/refractory Non-Hodgkin Lymphoma [EHA-2188].

  RESULT

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse

Interventions

zanubrutinib; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2018
• First Posted: May 11, 2018
• Study Start: January 4, 2018
• Primary Completion: August 28, 2020
• Study Completion: August 28, 2020
• Last Updated: October 26, 2024
• Results First Posted: October 28, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (4)