A Study to Investigate Zanubrutinib in Chinese Participants With B-cell Lymphoma

Sponsor
BeiGene (Industry)
Overall Status
Completed
CT.gov ID
NCT03189524
Collaborator
(none)
44
Enrollment
4
Locations
3
Arms
49.7
Actual Duration (Months)
11
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I clinical study was to investigate the safety, tolerability, and pharmacokinetics/pharmacodynamics of Bruton tyrosine kinase (BTK) inhibitor zanubrutinib (BGB-3111) in Chinese participants with B-cell lymphoma by conducting in two stages, the first stage being the safety assessment of dose and the second stage being the dose expansion.

Part I: Safety evaluation - according to the results of preclinical toxicological trials and the results of the phase I clinical study conducted in Australia and New Zealand, two regimens of zanubrutinib 320 milligrams (mg) daily (160 mg twice daily [BID]), administered in the morning and at night, or 320 mg once daily [QD]) and "3+3" design was adopted for the assessment. The recommended dose and method of administration of the phase II clinical study was determined according to the Part I results.

Part II: Dose expansion - this stage was to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL), approximately 20 participants with relapsed or refractory FL or MZL were to be enrolled. The recommended Phase 2 dose (RP2D) was used in Part II.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
44 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Clinical Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of BTK Inhibitor BGB-3111 in Chinese Patients With B-cell Lymphoma
Actual Study Start Date :
Jul 5, 2016
Actual Primary Completion Date :
Aug 26, 2020
Actual Study Completion Date :
Aug 26, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part I: 160 mg BID

Safety Evaluation: Two regimens of zanubrutinib 320 milligrams (mg) daily (160 mg twice daily [BID]) administered in the morning and at night, or 320 mg (once daily [QD]), and a "3+3" design was adopted for Part I of the study to determine recommended Phase 2 dose (RP2D).

Drug: Zanubrutinib
Zanubrutinib is a white to off-white solid that is slightly hygroscopic. The drug product was formulated as 20-mg (blue, size 3) and 80-mg (white, size 0) hard gelatin, opaque oral capsules. Zanubrutinib is classified as a Biopharmaceutics Classification System Class II compound.
Other Names:
  • BGB-3111
  • Experimental: Part I: 320 mg QD

    Safety Evaluation: Two regimens of zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night, or 320 mg QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.

    Drug: Zanubrutinib
    Zanubrutinib is a white to off-white solid that is slightly hygroscopic. The drug product was formulated as 20-mg (blue, size 3) and 80-mg (white, size 0) hard gelatin, opaque oral capsules. Zanubrutinib is classified as a Biopharmaceutics Classification System Class II compound.
    Other Names:
  • BGB-3111
  • Experimental: Part II: 160 mg BID

    Dose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL).

    Drug: Zanubrutinib
    Zanubrutinib is a white to off-white solid that is slightly hygroscopic. The drug product was formulated as 20-mg (blue, size 3) and 80-mg (white, size 0) hard gelatin, opaque oral capsules. Zanubrutinib is classified as a Biopharmaceutics Classification System Class II compound.
    Other Names:
  • BGB-3111
  • Outcome Measures

    Primary Outcome Measures

    1. Part I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events [From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)]

      All adverse events were treatment emergent and were defined as an adverse event with a reported onset time or increase in severity after the initial dose of study drug and within 30 days after the last dose of study drug or initiation of new anticancer therapy, whichever was sooner. A serious adverse event was any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is significant medical event requiring intervention. All toxicity and adverse events were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) grading criteria. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

    2. Part II: Overall Response Rate (ORR) Of Zanubrutinib In Participants With FL And MZL [Up to 4 years and 1 month]

      Overall response in overall response rate (ORR) was defined as a participant's best overall response: CR or PR for NHL participants; CR, complete remission with incomplete blood count recovery, nodular PR, PR, or PR with lymphocytosis for the CLL participants; CR, very good PR, PR, or minor response for the Waldenström macroglobulinemia participants. ORR was defined as the percentage of participants who achieved an overall response.

    3. Part II: Complete Response Rate (CRR) Of Zanubrutinib In Participants With FL And MZL [Up to 4 years and 1 month]

      CRR was defined as the percentage of participants who achieved CR as the best overall response.

    4. Part II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL [Up to 4 years and 1 month]

      PRR was defined as the percentage of participants who achieved PR or higher as the best overall response.

    5. Part II: Duration of Response (DOR) Of Zanubrutinib In Participants With FL And MZL [Up to 4 years and 1 month]

      Duration of response for responders (those who achieved an overall response of PR or better) was defined as the time interval (in number of days) between the date of the earliest qualifying response and the date of progressive disease or death for any cause (whichever occurs earlier). Duration of response analysis included only responders.

    6. Part II: Progression Free Survival (PFS) Of Zanubrutinib In Participants With FL And MZL [Up to 4 years and 1 month]

      Progression-free survival was defined as the time (in months) from the date of first study treatment to disease progression or death (due to any cause), whichever occurred first. For purposes of calculating PFS, the start date of progressive disease was the date at which progression was first observed. The duration and primary analysis of PFS was right-censored for participants who met 1 of the following conditions: 1) no baseline disease assessments; 2) starting a new anticancer therapy before documentation of disease progression or death; 3) death or disease progression immediately after more than 1 consecutively missed disease assessment visit; and 4) alive without documentation of disease progression before the data cutoff date.

    Secondary Outcome Measures

    1. Part I and Part II: Area Under The Plasma Concentration-time Curve From Zero To The Last Measurable Concentration (AUClast) For Single-dose Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    2. Part I and Part II: Area Under The Plasma Concentration-time Curve Zero To Infinity (AUC0-inf) For Single-dose Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    3. Part I And Part II: Maximum Plasma Concentration (Cmax) For Single-dose Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    4. Part I and Part II: Time To Maximum Plasma Concentration (Tmax) For Single-dose Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    5. Part I and Part II: Apparent Terminal Half Life (t1/2) For Single-dose Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    6. Part I and Part II: Apparent Plasma Clearance (CL/F) For Single-dose Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    7. Part I and Part II: Terminal Apparent Volume Of Distribution (Vz/F) For Single-dose Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    8. Part I and Part II: Area Under The Plasma Concentration-time Curve For Steady State (AUCss) Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    9. Part I and Part II: Maximum Plasma Concentration At Steady State (Cmax,ss) For Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    10. Part I and Part II: Time To Steady Plasma Concentration (Tmax,ss) For Zanubrutinib [Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose]

    11. Part I: Percentage of BTK Occupied In Peripheral Blood Mononuclear Cells In Participants Who Received Zanubrutinib [DLT Period: Days 1 and 2 of Week 1 and Day 1 of Week 2]

      The percentage of BTK occupied in peripheral blood mononuclear cells was evaluated as a biomarker for the inhibition of BTK on specified days and the average value is reported.

    12. Part II: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events [From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)]

      All adverse events are treatment emergent, defined as an adverse event with a reported onset time or increase in severity after the initial dose of study drug and within 30 days after the last dose of study drug or initiation of new anticancer therapy, whichever was sooner. A serious adverse event was any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is significant medical event requiring intervention. All toxicity and adverse events were assessed according to the NCI-CTCAE v4.03 grading criteria. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • Men and women between the age of 18-75 years.

    • Participants with B-cell lymphoma (defined by World Health Organization classification) refractory or relapsed following at least one line of therapy.

    • Judged by the investigator as requiring treatment.

    • Eastern Cooperative Oncology Group performance status of 0-1.

    • Life expectancy of at least 4 months.

    • Adequate hematological function.

    • Adequate renal function.

    • Adequate liver function.

    • Adequate coagulation function.

    • Female participants of childbearing potential and non-sterile males must have practiced at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, intrauterine device or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.

    • Male participants must not have donated sperm from start of study drug administration, until 90 days after discontinuation of treatment.

    Key Exclusion Criteria:
    • With central nervous system involvement of the disease.

    • The pathological type of the disease had disease transformation.

    • Had underdone allogeneic hematopoietic stem cell transplantation.

    • Had received corticosteroid anti-neoplastic treatment within 7 days before the first dose, has received radiotherapy and chemotherapy within 4 weeks before the first dose or has received treatment with monoclonal antibody within 4 weeks before the first dose.

    • Had received BTK inhibitor treatment prior to enrollment.

    • Had received chemotherapy and has not yet recovered from toxicity

    • Had received Chinese herbal medicine as anti-neoplastic therapy within 4 weeks before starting study treatment.

    • History of other malignancies within 2 years before study.

    • With uncontrolled systemic infection.

    • Major surgery in the past 4 weeks.

    • With known HIV, or active hepatitis B or hepatitis C virus infection.

    • With cardiovascular disease of New York Heart Association Classification ≥ 3.

    • Significant electrocardiogram abnormalities.

    • Significant active renal, neurologic, psychiatric, hepatic or endocrinologic disease that in the investigator's opinion would adversely impact on his/her participation in the study.

    • Inability to comply with study procedures.

    • Was currently taking anticoagulant drugs.

    • Was currently taking potent cytochrome P450 3A inhibitor or inducer.

    • Had stroke or cerebral hemorrhage within 6 months before enrollment.

    Note: Other protocol defined Inclusion/Exclusion criteria may have applied.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Beijing Cancer HospitalBeijingBeijingChina100142
    2Tongji Hospital, Tongji Medical College Huazhong University of Science and TechnologyWuhanHubeiChina
    3Jiangsu Province HospitalNanjingJiangsuChina
    4Tianjin Hematonosis HospitalTianjinTianjinChina

    Sponsors and Collaborators

    • BeiGene

    Investigators

    • Principal Investigator: Study Director, BeiGene

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    BeiGene
    ClinicalTrials.gov Identifier:
    NCT03189524
    Other Study ID Numbers:
    • BGB-3111-1002
    • CTR20160204
    First Posted:
    Jun 16, 2017
    Last Update Posted:
    Oct 22, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsThis study was conducted at 4 centers in China, all of which enrolled participants. The first participant was dosed on 05 July 2016. As of the final database lock (15 October 2020), 44 participants were enrolled and treated with zanubrutinib (BGB-3111). Once the final analysis was completed, the study was terminated and all participants who were still on treatment were transferred to long term extension study.
    Pre-assignment Detail
    Arm/Group TitlePart I: 160 mg BIDPart I: 320 mg QDPart II: 160 mg BID
    Arm/Group DescriptionSafety Evaluation: The participants in this dose regimen received zanubrutinib 320 milligrams (mg) (160 mg twice daily [BID], administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D.Safety Evaluation: The participants in this dose regimen received zanubrutinib 320 mg daily (320 mg once daily [QD]) and a "3+3" design was adopted for Part I of the study to determine RP2D.Dose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL).
    Period Title: Overall Study
    STARTED111023
    Received at Least 1 Dose of Study Drug111023
    COMPLETED000
    NOT COMPLETED111023

    Baseline Characteristics

    Arm/Group TitlePart I: 160 mg BIDPart I: 320 mg QDPart II: 160 mg BIDTotal
    Arm/Group DescriptionSafety Evaluation: The participants in this dose regimen received zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D.Safety Evaluation: The participants in this dose regimen received zanubrutinib 320 mg daily (320 mg QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.Dose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Total of all reporting groups
    Overall Participants11102344
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51.9
    (10.65)
    52.1
    (10.57)
    48.4
    (11.85)
    50.1
    (11.18)
    Sex: Female, Male (Count of Participants)
    Female
    2
    18.2%
    3
    30%
    15
    65.2%
    20
    45.5%
    Male
    9
    81.8%
    7
    70%
    8
    34.8%
    24
    54.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    11
    100%
    10
    100%
    23
    100%
    44
    100%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitlePart I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
    DescriptionAll adverse events were treatment emergent and were defined as an adverse event with a reported onset time or increase in severity after the initial dose of study drug and within 30 days after the last dose of study drug or initiation of new anticancer therapy, whichever was sooner. A serious adverse event was any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is significant medical event requiring intervention. All toxicity and adverse events were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) grading criteria. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
    Time FrameFrom the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set: Included all participants who received ≥ 1 dose of zanubrutinib. The Safety Analysis Set was used for all summaries (except DLT and PK).
    Arm/Group TitlePart I: 160 mg BIDPart I: 320 mg QD
    Arm/Group DescriptionSafety Evaluation: The participants in this dose regimen received zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D.Safety Evaluation: The participants in this dose regimen received zanubrutinib 320 mg daily (320 mg QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants1110
    Participants with ≥ 1 adverse event
    11
    100%
    10
    100%
    Participants with serious adverse events
    2
    18.2%
    2
    20%
    2. Primary Outcome
    TitlePart II: Overall Response Rate (ORR) Of Zanubrutinib In Participants With FL And MZL
    DescriptionOverall response in overall response rate (ORR) was defined as a participant's best overall response: CR or PR for NHL participants; CR, complete remission with incomplete blood count recovery, nodular PR, PR, or PR with lymphocytosis for the CLL participants; CR, very good PR, PR, or minor response for the Waldenström macroglobulinemia participants. ORR was defined as the percentage of participants who achieved an overall response.
    Time FrameUp to 4 years and 1 month

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set: Included all participants who received ≥ 1 dose of zanubrutinib. The Safety Analysis Set was used for all summaries (except DLT and PK).
    Arm/Group TitlePart II: 160 mg BID
    Arm/Group DescriptionDose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.
    Measure Participants23
    Number (95% Confidence Interval) [Percentage of Participants]
    30.4
    276.4%
    3. Primary Outcome
    TitlePart II: Complete Response Rate (CRR) Of Zanubrutinib In Participants With FL And MZL
    DescriptionCRR was defined as the percentage of participants who achieved CR as the best overall response.
    Time FrameUp to 4 years and 1 month

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set: Included all participants who received ≥ 1 dose of zanubrutinib. The Safety Analysis Set was used for all summaries (except DLT and PK).
    Arm/Group TitlePart II: 160 mg BID
    Arm/Group DescriptionDose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.
    Measure Participants23
    Number (95% Confidence Interval) [Percentage of Participants]
    13
    118.2%
    4. Primary Outcome
    TitlePart II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL
    DescriptionPRR was defined as the percentage of participants who achieved PR or higher as the best overall response.
    Time FrameUp to 4 years and 1 month

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set: Included all participants who received ≥ 1 dose of zanubrutinib. The Safety Analysis Set was used for all summaries (except DLT and PK).
    Arm/Group TitlePart II: 160 mg BID
    Arm/Group DescriptionDose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.
    Measure Participants23
    Number (95% Confidence Interval) [Percentage of Participants]
    30.4
    276.4%
    5. Primary Outcome
    TitlePart II: Duration of Response (DOR) Of Zanubrutinib In Participants With FL And MZL
    DescriptionDuration of response for responders (those who achieved an overall response of PR or better) was defined as the time interval (in number of days) between the date of the earliest qualifying response and the date of progressive disease or death for any cause (whichever occurs earlier). Duration of response analysis included only responders.
    Time FrameUp to 4 years and 1 month

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set: Included all participants who received ≥ 1 dose of zanubrutinib. The Safety Analysis Set was used for all summaries (except DLT and PK).
    Arm/Group TitlePart II: 160 mg BID
    Arm/Group DescriptionDose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.
    Measure Participants23
    Median (95% Confidence Interval) [Months]
    11.2
    6. Primary Outcome
    TitlePart II: Progression Free Survival (PFS) Of Zanubrutinib In Participants With FL And MZL
    DescriptionProgression-free survival was defined as the time (in months) from the date of first study treatment to disease progression or death (due to any cause), whichever occurred first. For purposes of calculating PFS, the start date of progressive disease was the date at which progression was first observed. The duration and primary analysis of PFS was right-censored for participants who met 1 of the following conditions: 1) no baseline disease assessments; 2) starting a new anticancer therapy before documentation of disease progression or death; 3) death or disease progression immediately after more than 1 consecutively missed disease assessment visit; and 4) alive without documentation of disease progression before the data cutoff date.
    Time FrameUp to 4 years and 1 month

    Outcome Measure Data

    Analysis Population Description
    Safety Analysis Set: Included all participants who received ≥ 1 dose of zanubrutinib. The Safety Analysis Set was used for all summaries (except DLT and PK).
    Arm/Group TitlePart II: 160 mg BID
    Arm/Group DescriptionDose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.
    Measure Participants23
    Median (95% Confidence Interval) [Months]
    5.5
    7. Secondary Outcome
    TitlePart I and Part II: Area Under The Plasma Concentration-time Curve From Zero To The Last Measurable Concentration (AUClast) For Single-dose Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed.
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants3410
    Mean (Standard Deviation) [nanogram/milliliter*hour]
    981.6
    (619.6)
    1404
    (560.7)
    8. Secondary Outcome
    TitlePart I and Part II: Area Under The Plasma Concentration-time Curve Zero To Infinity (AUC0-inf) For Single-dose Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants329
    Mean (Standard Deviation) [nanogram/milliliter*hour]
    1025
    (633.5)
    1537
    (519.0)
    9. Secondary Outcome
    TitlePart I And Part II: Maximum Plasma Concentration (Cmax) For Single-dose Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants3410
    Mean (Standard Deviation) [nanogram/milliliter]
    319
    (217)
    409
    (149)
    10. Secondary Outcome
    TitlePart I and Part II: Time To Maximum Plasma Concentration (Tmax) For Single-dose Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants3410
    Median (Full Range) [hour]
    2.00
    2.50
    11. Secondary Outcome
    TitlePart I and Part II: Apparent Terminal Half Life (t1/2) For Single-dose Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants329
    Mean (Standard Deviation) [hour]
    2.27
    (1.21)
    3.43
    (2.23)
    12. Secondary Outcome
    TitlePart I and Part II: Apparent Plasma Clearance (CL/F) For Single-dose Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed. Participants with available data were included in the analysis.
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants329
    Mean (Standard Deviation) [liter/hour]
    251
    (194)
    235
    (93.7)
    13. Secondary Outcome
    TitlePart I and Part II: Terminal Apparent Volume Of Distribution (Vz/F) For Single-dose Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed. Participants with available data were included in the analysis.
    Arm/Group Title160 mg320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants329
    Mean (Standard Deviation) [liter]
    713
    (512)
    1120
    (738)
    14. Secondary Outcome
    TitlePart I and Part II: Area Under The Plasma Concentration-time Curve For Steady State (AUCss) Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed. Participants with available data were included in the analysis.
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants338
    Mean (Standard Deviation) [nanogram/milliliter*hour]
    738.3
    (425.2)
    1277
    (607.4)
    15. Secondary Outcome
    TitlePart I and Part II: Maximum Plasma Concentration At Steady State (Cmax,ss) For Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set included all participants who received ≥ 1 dose of zanubrutinib. The analysis was pre-specified to be a pooled analysis by dose level; therefore, data by individual arms was not analyzed. Participants with available data were included in the analysis.
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants3310
    Mean (Standard Deviation) [nanogram/milliliter]
    257
    (147)
    389
    (185)
    16. Secondary Outcome
    TitlePart I and Part II: Time To Steady Plasma Concentration (Tmax,ss) For Zanubrutinib
    Description
    Time FramePart 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title160 mg BID320 mg QD
    Arm/Group DescriptionPart I: Zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D. Part II: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.Part I: Zanubrutinib 320 mg daily (QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants3310
    Median (Full Range) [hour]
    2.00
    2.0
    17. Secondary Outcome
    TitlePart I: Percentage of BTK Occupied In Peripheral Blood Mononuclear Cells In Participants Who Received Zanubrutinib
    DescriptionThe percentage of BTK occupied in peripheral blood mononuclear cells was evaluated as a biomarker for the inhibition of BTK on specified days and the average value is reported.
    Time FrameDLT Period: Days 1 and 2 of Week 1 and Day 1 of Week 2

    Outcome Measure Data

    Analysis Population Description
    DLT Evaluable Set: Included all participants who received ≥ 75% of the planned doses of treatment during the DLT observation period (Day 28).Only participants with sufficient sample availability were used in the analysis.
    Arm/Group TitlePart I: 160 mg BID or 320 mg QD
    Arm/Group DescriptionSafety Evaluation: The participants in this dose regimen received zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) or 320 mg QD and a "3+3" design was adopted for Part I of the study to determine RP2D.
    Measure Participants13
    Mean (Standard Deviation) [Percentage]
    96.69
    (5.297)
    18. Secondary Outcome
    TitlePart II: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
    DescriptionAll adverse events are treatment emergent, defined as an adverse event with a reported onset time or increase in severity after the initial dose of study drug and within 30 days after the last dose of study drug or initiation of new anticancer therapy, whichever was sooner. A serious adverse event was any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is significant medical event requiring intervention. All toxicity and adverse events were assessed according to the NCI-CTCAE v4.03 grading criteria. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
    Time FrameFrom the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePart II: 160 mg BID
    Arm/Group DescriptionDose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.
    Measure Participants23
    Participants with ≥ 1 adverse event
    22
    200%
    Participants with serious adverse events
    5
    45.5%

    Adverse Events

    Time FrameFrom the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
    Adverse Event Reporting Description
    Arm/Group TitlePart I: 160 mg BIDPart I: 320 mg QDPart II: 160 mg BID
    Arm/Group DescriptionSafety Evaluation: The participants in this dose regimen received zanubrutinib 320 mg daily (160 mg BID, administered in the morning and at night) and a "3+3" design was adopted for Part I of the study to determine RP2D.Safety Evaluation: The participants in this dose regimen received zanubrutinib 320 mg daily (320 mg QD) and a "3+3" design was adopted for Part I of the study to determine RP2D.Dose Expansion: The RP2D determined in Part I was used in Part II to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with FL or MZL.
    All Cause Mortality
    Part I: 160 mg BIDPart I: 320 mg QDPart II: 160 mg BID
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/11 (18.2%) 3/10 (30%) 1/23 (4.3%)
    Serious Adverse Events
    Part I: 160 mg BIDPart I: 320 mg QDPart II: 160 mg BID
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/11 (18.2%) 2/10 (20%) 5/23 (21.7%)
    Blood and lymphatic system disorders
    Anaemia0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Febrile neutropenia0/11 (0%) 1/10 (10%) 0/23 (0%)
    Lymphadenopathy0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Gastrointestinal disorders
    Ascites0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    General disorders
    Fatigue0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Infections and infestations
    Pleural infection0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Pneumonia0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Investigations
    Neutrophil count decreased0/11 (0%) 1/10 (10%) 0/23 (0%)
    Platelet count decreased0/11 (0%) 1/10 (10%) 0/23 (0%)
    Metabolism and nutrition disorders
    Hyperglycaemia0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cholesterin granuloma of middle ear1/11 (9.1%) 0/10 (0%) 0/23 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Skin and subcutaneous tissue disorders
    Toxic epidermal necrolysis1/11 (9.1%) 0/10 (0%) 0/23 (0%)
    Surgical and medical procedures
    Abortion induced0/11 (0%) 0/10 (0%) 1/23 (4.3%)
    Other (Not Including Serious) Adverse Events
    Part I: 160 mg BIDPart I: 320 mg QDPart II: 160 mg BID
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total11/11 (100%) 10/10 (100%) 22/23 (95.7%)
    Blood and lymphatic system disorders
    Anaemia4/11 (36.4%) 4/10 (40%) 8/23 (34.8%)
    Neutropenia3/11 (27.3%) 1/10 (10%) 2/23 (8.7%)
    Platelet dysfunction3/11 (27.3%) 1/10 (10%) 2/23 (8.7%)
    Hypofibrinogenaemia1/11 (9.1%) 1/10 (10%) 2/23 (8.7%)
    Thrombocytopenia1/11 (9.1%) 1/10 (10%) 1/23 (4.3%)
    Leukopenia1/11 (9.1%) 0/10 (0%) 1/23 (4.3%)
    Gastrointestinal disorders
    Constipation1/11 (9.1%) 1/10 (10%) 3/23 (13%)
    Diarrhoea2/11 (18.2%) 1/10 (10%) 0/23 (0%)
    Abdominal pain0/11 (0%) 0/10 (0%) 2/23 (8.7%)
    Abdominal pain upper0/11 (0%) 1/10 (10%) 1/23 (4.3%)
    Mouth ulceration0/11 (0%) 2/10 (20%) 0/23 (0%)
    Nausea0/11 (0%) 0/10 (0%) 2/23 (8.7%)
    Stomatitis2/11 (18.2%) 0/10 (0%) 0/23 (0%)
    General disorders
    Pyrexia1/11 (9.1%) 3/10 (30%) 1/23 (4.3%)
    Asthenia1/11 (9.1%) 1/10 (10%) 0/23 (0%)
    Fatigue2/11 (18.2%) 0/10 (0%) 0/23 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia1/11 (9.1%) 2/10 (20%) 1/23 (4.3%)
    Infections and infestations
    Upper respiratory tract infection5/11 (45.5%) 5/10 (50%) 5/23 (21.7%)
    Pneumonia3/11 (27.3%) 3/10 (30%) 3/23 (13%)
    Nasopharyngitis5/11 (45.5%) 1/10 (10%) 0/23 (0%)
    Urinary tract infection0/11 (0%) 1/10 (10%) 3/23 (13%)
    Pharyngitis0/11 (0%) 2/10 (20%) 1/23 (4.3%)
    Gingivitis0/11 (0%) 1/10 (10%) 1/23 (4.3%)
    Investigations
    Neutrophil count decreased8/11 (72.7%) 7/10 (70%) 9/23 (39.1%)
    White blood cell count decreased3/11 (27.3%) 3/10 (30%) 9/23 (39.1%)
    Platelet count decreased4/11 (36.4%) 2/10 (20%) 4/23 (17.4%)
    Weight increased2/11 (18.2%) 3/10 (30%) 3/23 (13%)
    Alanine aminotransferase increased2/11 (18.2%) 2/10 (20%) 0/23 (0%)
    Aspartate aminotransferase increased1/11 (9.1%) 2/10 (20%) 1/23 (4.3%)
    Blood creatinine increased0/11 (0%) 2/10 (20%) 2/23 (8.7%)
    Weight decreased0/11 (0%) 1/10 (10%) 3/23 (13%)
    White blood cells urine positive1/11 (9.1%) 1/10 (10%) 2/23 (8.7%)
    Blood alkaline phosphatase increased0/11 (0%) 1/10 (10%) 2/23 (8.7%)
    Blood lactate dehydrogenase increased2/11 (18.2%) 1/10 (10%) 0/23 (0%)
    Blood urine present0/11 (0%) 1/10 (10%) 2/23 (8.7%)
    White blood cell count increased0/11 (0%) 1/10 (10%) 2/23 (8.7%)
    Blood fibrinogen decreased2/11 (18.2%) 0/10 (0%) 0/23 (0%)
    Blood potassium decreased1/11 (9.1%) 0/10 (0%) 1/23 (4.3%)
    Electrocardiogram QT prolonged1/11 (9.1%) 1/10 (10%) 0/23 (0%)
    Gamma-glutamyltransferase increased1/11 (9.1%) 1/10 (10%) 0/23 (0%)
    Haemoglobin decreased1/11 (9.1%) 0/10 (0%) 1/23 (4.3%)
    Lymphocyte count increased0/11 (0%) 2/10 (20%) 0/23 (0%)
    Metabolism and nutrition disorders
    Hyperuricaemia2/11 (18.2%) 3/10 (30%) 5/23 (21.7%)
    Hypercholesterolaemia1/11 (9.1%) 1/10 (10%) 3/23 (13%)
    Hypertriglyceridaemia1/11 (9.1%) 2/10 (20%) 2/23 (8.7%)
    Hyperglycaemia1/11 (9.1%) 1/10 (10%) 1/23 (4.3%)
    Hypoalbuminaemia1/11 (9.1%) 0/10 (0%) 1/23 (4.3%)
    Hypocalcaemia1/11 (9.1%) 1/10 (10%) 0/23 (0%)
    Hypokalaemia1/11 (9.1%) 0/10 (0%) 1/23 (4.3%)
    Psychiatric disorders
    Insomnia1/11 (9.1%) 1/10 (10%) 0/23 (0%)
    Renal and urinary disorders
    Haematuria4/11 (36.4%) 3/10 (30%) 2/23 (8.7%)
    Haemoglobinuria2/11 (18.2%) 1/10 (10%) 3/23 (13%)
    Proteinuria2/11 (18.2%) 1/10 (10%) 2/23 (8.7%)
    Leukocyturia0/11 (0%) 1/10 (10%) 1/23 (4.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough3/11 (27.3%) 3/10 (30%) 2/23 (8.7%)
    Dyspnoea1/11 (9.1%) 0/10 (0%) 1/23 (4.3%)
    Laryngeal pain0/11 (0%) 2/10 (20%) 0/23 (0%)
    Oropharyngeal pain1/11 (9.1%) 1/10 (10%) 0/23 (0%)
    Skin and subcutaneous tissue disorders
    Rash3/11 (27.3%) 2/10 (20%) 5/23 (21.7%)
    Purpura2/11 (18.2%) 2/10 (20%) 1/23 (4.3%)
    Rash maculo-papular2/11 (18.2%) 3/10 (30%) 0/23 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights.

    Results Point of Contact

    Name/TitleStudy Director
    OrganizationBeiGene
    Phone+1-877-828-5568
    Emailclinicaltrials@beigene.com
    Responsible Party:
    BeiGene
    ClinicalTrials.gov Identifier:
    NCT03189524
    Other Study ID Numbers:
    • BGB-3111-1002
    • CTR20160204
    First Posted:
    Jun 16, 2017
    Last Update Posted:
    Oct 22, 2021
    Last Verified:
    Sep 1, 2021