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

• ClinicalTrials.gov Identifier: NCT03206970
• Recruitment Status: Completed
• First Posted: July 2, 2017
• Results First Posted: May 13, 2020
• Last Update Posted: November 5, 2021
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Refractory Mantle Cell Lymphoma; Relapsed Mantle Cell Lymphoma	Drug: Zanubrutinib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 86 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: March 2, 2017
• Actual Primary Completion Date: February 15, 2019
• Actual Study Completion Date: September 8, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) As Assessed By Independent Review Committee [ Time Frame: Up to 1 year and 11 months ]
   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.

Secondary Outcome Measures :

1. Progression-free Survival [ Time Frame: Up to 3 years and 6 months ]
   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.
2. Time To Response [ Time Frame: Up to 3 years and 6 months ]
   Time to response was defined as the time from treatment initiation to the first documentation of response.
3. Duration Of Response [ Time Frame: Up to 3 years and 6 months ]
   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.
4. ORR As Assessed By The Investigator [ Time Frame: Up to 3 years and 6 months ]
   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.
5. Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs) [ Time Frame: From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months) ]

   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.

6. Number Of Participants Experiencing AEs Leading To Treatment Discontinuation [ Time Frame: From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China, Beijing

Beijing Cancer Hospital

Beijing, Beijing, China, 100142

Peking Union Medical College Hospital

Beijing, Beijing, China

China, Fujian

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

China, Guangdong

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

China, Henan

Henan Cancer Province

Zhengzhou, Henan, China

China, Hubei

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

Wuhan, Hubei, China

China, Jiangsu

Jiangsu Province Hospital

Nanjing, Jiangsu, China

China, Jilin

The First Affiliated Hospital of Jinlin University

Chang chun, Jilin, China

China, Shanghai

Fudan University Cancer Center

Shanghai, Shanghai, China

China, Sichuan

West China Hospital, Sichuan University

Chengdu, Sichuan, China

China, Tianjin

Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin, China

Tianjin Cancer Hospital

Tianjin, Tianjin, China

China, Zhejiang

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Sponsors and Collaborators

BeiGene

Investigators

• Principal Investigator: Study Director; BeiGene

  Study Documents (Full-Text)

Documents provided by BeiGene:

Study Protocol  [PDF] September 6, 2018

Statistical Analysis Plan  [PDF] April 2, 2018

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT03206970
• Other Study ID Numbers: BGB-3111-206; CTR20160888 ( Registry Identifier: Center for drug evaluation, CFDA )
• First Posted: July 2, 2017
• Results First Posted: May 13, 2020
• Last Update Posted: November 5, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Mantle-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Zanubrutinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action