Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate Efficacy and Safety of BGB-3111, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Subjects With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

The primary objective of this study was to evaluate the efficacy of zanubrutinib in participants with centrally confirmed relapsed or refractory MCL.

Study Overview

• Status: Completed
• Conditions: Refractory Mantle Cell Lymphoma; Relapsed Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Zanubrutinib

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer hospital
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital of Southern Medical University
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Province
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
  • Jilin
    • Chang chun, Jilin, China
      • The First Affiliated Hospital of Jinlin University
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Cancer Center
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China
      • Blood Diseases Hospital, Chinese Academy of medical Sciences
    • Tianjin, Tianjin, China
      • Tianjin Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Diagnostic report had to include evidence for morphological and cyclin D1 or t (11; 14).
2. Eastern Cooperative Oncology Group performance status of 0-2.
3. Measurable disease by computed tomography/magnetic resonance imaging.
4. Received prior regimens for MCL.
5. Documented failure to achieve any response, (stable disease or progressive disease during treatment) or documented progressive disease after response to the most recent treatment regimen.
6. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN).
7. Total bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).
8. Life expectancy of > 4 months.

Key Exclusion Criteria:

1. Current or history of central nervous system lymphoma.
2. Prior exposure to a BTK inhibitor before enrollment.
3. Prior corticosteroids with anti-neoplastic intent within 7 days.
4. Major surgery within 4 weeks of screening.
5. Toxicity must have recovered from prior chemotherapy.
6. History of other active malignancies within 2 years of study entry.
7. Currently clinically significant active cardiovascular disease.
8. QT interval corrected with Fridericia's formula > 450 microseconds or other significant electrocardiogram abnormalities.
9. Uncontrolled systemic infection or infection requiring parenteral anti-microbial therapy.
10. Known human immunodeficiency virus infection, or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction).

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib; Zanubrutinib (160 milligrams) administered orally twice daily	Drug: Zanubrutinib; Administered as specified in the treatment arm.; Other Names: BGB-3111

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) As Assessed By Independent Review Committee	The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR.	Up to 1 year and 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival was defined as the time from the starting date of zanubrutinib to the date of first documentation of disease progression or death, whichever occurred first. Participants who did not have disease progression were censored at their last valid tumor assessment. A six-month progression-free survival rate was defined as no disease progression after treated with zanubrutinib for over six months (under control). The 95% confidence interval (CI) lower bound was 33.1 months while the upper bound could not be estimated.	Up to 3 years and 6 months
Time To Response	Time to response was defined as the time from treatment initiation to the first documentation of response.	Up to 3 years and 6 months
Duration Of Response	The duration of response was defined as the time from the date that the response criteria are first met to the date that Progressive Disease was objectively documented or death (whichever occurs first). Participants who did not have disease progression were censored at their last valid assessment.	Up to 3 years and 6 months
ORR As Assessed By The Investigator	The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a BOR of CR or PR. The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR. For this outcome measure, only investigator-assessed data are analyzed and reported because of the high rate of concordance between the Independent Review Committee and investigator assessments for the primary outcome measure of ORR.	Up to 3 years and 6 months
Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs)	An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up visit) or initiation of new anticancer therapy, whichever comes first.	From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)
Number Of Participants Experiencing AEs Leading To Treatment Discontinuation	An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to the study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.	From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)

Collaborators and Investigators

• Sponsor: BeiGene

Publications and helpful links

General Publications

• Yuqin Song, Keshu Zhou, Dehui Zou, Jianfeng Zhou, Jianda Hu, Haiyan Yang, Huilai Zhang, Jie Ji, Wei Xu, Jie Jin, Fangfang Lv, Ru Feng, Sujun Gao, Daobin Zhou, Haiyi Guo, Aihua Wang, James Hilger, Jane Huang, William Novotny, Muhtar Osman, Jun Zhu; Safety and Activity of the Investigational Bruton Tyrosine Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Mantle Cell Lymphoma from a Phase 2 Trial. Blood 2018; 132 (Supplement 1): 148. doi: https://doi.org/10.1182/blood-2018-99-117956
• Song Y, Zhou K, Zou D, Zhou J, Hu J, Yang H, Zhang H, Ji J, Xu W, Jin J, Lv F, Feng R, Gao S, Guo H, Zhou L, Elstrom R, Huang J, Novotny W, Wei R, Zhu J. Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. Clin Cancer Res. 2020 Aug 15;26(16):4216-4224. doi: 10.1158/1078-0432.CCR-19-3703. Epub 2020 May 27.
• Tam CS, Opat S, Simpson D, Cull G, Munoz J, Phillips TJ, Kim WS, Rule S, Atwal SK, Wei R, Novotny W, Huang J, Wang M, Trotman J. Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Blood Adv. 2021 Jun 22;5(12):2577-2585. doi: 10.1182/bloodadvances.2020004074.
• Song Y, Zhou K, Zou D, Zhou J, Hu J, Yang H, Zhang H, Ji J, Xu W, Jin J, Lv F, Feng R, Gao S, Guo H, Zhou L, Huang J, Novotny W, Kim P, Yu Y, Wu B, Zhu J. Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. Blood. 2022 May 26;139(21):3148-3158. doi: 10.1182/blood.2021014162.

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2017
• Primary Completion (Actual): February 15, 2019
• Study Completion (Actual): September 8, 2020

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: October 8, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: BGB-3111-206; CTR20160888 (Registry Identifier: Center for drug evaluation, CFDA)

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: No
• Studies a U.S. FDA-regulated device product: No