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

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

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 Disease	Intervention/Treatment	Phase
B-cell Lymphoma	Drug: Zanubrutinib	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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	Beijing Cancer Hospital	Beijing	Beijing	China	100142
2	Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei	China
3	Jiangsu Province Hospital	Nanjing	Jiangsu	China
4	Tianjin Hematonosis Hospital	Tianjin	Tianjin	China

Sponsors and Collaborators

• BeiGene

Investigators

• Principal Investigator: Study Director, BeiGene

Study Documents (Full-Text)

• Study Protocol - Feb 6, 2017
• Statistical Analysis Plan - Nov 1, 2017

More Information

Publications

• Jun Zhu, BS, Jianyong Li, MD, Jianfeng Zhou, Yuqin Song, MD, Junyuan Qi, Wei Xu, Dengju Li, MD, Mingyuan Sun, Ling Xue, PhD, Liudi Yang, Yinwei Zhang, Lai Wang, PhD, Jane Huang, MD, Shibao Feng, PhD, Lugui Qiu, MD. BGB-3111, a Highly Specific BTK Inhibitor, Is Well Tolerated and Highly Active in Chinese Patients with Relapsed/Refractory B-Cell Malignancies: Initial Report of a Phase 1 Trial in China. Blood. 2017; 130(1): 5347. https://doi.org/10.1182/blood.V130.Suppl_1.5347.5347

• 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: Lymphoma; Lymphoma, B-Cell; Zanubrutinib

Study Results

Participant Flow

Recruitment Details

This 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.

Arm/Group Title	Part I: 160 mg BID	Part I: 320 mg QD	Part II: 160 mg BID
Arm/Group Description	Safety 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
STARTED	11	10	23
Received at Least 1 Dose of Study Drug	11	10	23
COMPLETED	0	0	0
NOT COMPLETED	11	10	23

Baseline Characteristics

Arm/Group Title	Part I: 160 mg BID	Part I: 320 mg QD	Part II: 160 mg BID	Total
Arm/Group Description	Safety 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 Participants	11	10	23	44
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

Title	Part I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Description	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.
Time Frame	From 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 Title	Part I: 160 mg BID	Part I: 320 mg QD
Arm/Group Description	Safety 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 Participants	11	10
Participants with ≥ 1 adverse event	11 100%	10 100%
Participants with serious adverse events	2 18.2%	2 20%

2. Primary Outcome

Title	Part II: Overall Response Rate (ORR) Of Zanubrutinib In Participants With FL And MZL
Description	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.
Time Frame	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 Title	Part II: 160 mg BID
Arm/Group Description	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.
Measure Participants	23
Number (95% Confidence Interval) [Percentage of Participants]	30.4 276.4%

3. Primary Outcome

Title	Part II: Complete Response Rate (CRR) Of Zanubrutinib In Participants With FL And MZL
Description	CRR was defined as the percentage of participants who achieved CR as the best overall response.
Time Frame	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 Title	Part II: 160 mg BID
Arm/Group Description	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.
Measure Participants	23
Number (95% Confidence Interval) [Percentage of Participants]	13 118.2%

4. Primary Outcome

Title	Part II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL
Description	PRR was defined as the percentage of participants who achieved PR or higher as the best overall response.
Time Frame	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 Title	Part II: 160 mg BID
Arm/Group Description	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.
Measure Participants	23
Number (95% Confidence Interval) [Percentage of Participants]	30.4 276.4%

5. Primary Outcome

Title	Part II: Duration of Response (DOR) Of Zanubrutinib In Participants With FL And MZL
Description	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.
Time Frame	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 Title	Part II: 160 mg BID
Arm/Group Description	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.
Measure Participants	23
Median (95% Confidence Interval) [Months]	11.2

6. Primary Outcome

Title	Part II: Progression Free Survival (PFS) Of Zanubrutinib In Participants With FL And MZL
Description	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.
Time Frame	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 Title	Part II: 160 mg BID
Arm/Group Description	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.
Measure Participants	23
Median (95% Confidence Interval) [Months]	5.5

7. Secondary Outcome

Title	Part I and Part II: Area Under The Plasma Concentration-time Curve From Zero To The Last Measurable Concentration (AUClast) For Single-dose Zanubrutinib
Time Frame	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

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 Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	34	10
Mean (Standard Deviation) [nanogram/milliliter*hour]	981.6 (619.6)	1404 (560.7)

8. Secondary Outcome

Title	Part I and Part II: Area Under The Plasma Concentration-time Curve Zero To Infinity (AUC0-inf) For Single-dose Zanubrutinib
Time Frame	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

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 Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	32	9
Mean (Standard Deviation) [nanogram/milliliter*hour]	1025 (633.5)	1537 (519.0)

9. Secondary Outcome

Title	Part I And Part II: Maximum Plasma Concentration (Cmax) For Single-dose Zanubrutinib
Time Frame	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

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 Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	34	10
Mean (Standard Deviation) [nanogram/milliliter]	319 (217)	409 (149)

10. Secondary Outcome

Title	Part I and Part II: Time To Maximum Plasma Concentration (Tmax) For Single-dose Zanubrutinib
Time Frame	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

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 Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	34	10
Median (Full Range) [hour]	2.00	2.50

11. Secondary Outcome

Title	Part I and Part II: Apparent Terminal Half Life (t1/2) For Single-dose Zanubrutinib
Time Frame	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

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 Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	32	9
Mean (Standard Deviation) [hour]	2.27 (1.21)	3.43 (2.23)

12. Secondary Outcome

Title	Part I and Part II: Apparent Plasma Clearance (CL/F) For Single-dose Zanubrutinib
Time Frame	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

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 Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	32	9
Mean (Standard Deviation) [liter/hour]	251 (194)	235 (93.7)

13. Secondary Outcome

Title	Part I and Part II: Terminal Apparent Volume Of Distribution (Vz/F) For Single-dose Zanubrutinib
Time Frame	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

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 Title	160 mg	320 mg QD
Arm/Group Description	Part 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 Participants	32	9
Mean (Standard Deviation) [liter]	713 (512)	1120 (738)

14. Secondary Outcome

Title	Part I and Part II: Area Under The Plasma Concentration-time Curve For Steady State (AUCss) Zanubrutinib
Time Frame	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

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 Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	33	8
Mean (Standard Deviation) [nanogram/milliliter*hour]	738.3 (425.2)	1277 (607.4)

15. Secondary Outcome

Title	Part I and Part II: Maximum Plasma Concentration At Steady State (Cmax,ss) For Zanubrutinib
Time Frame	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

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 Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	33	10
Mean (Standard Deviation) [nanogram/milliliter]	257 (147)	389 (185)

16. Secondary Outcome

Title	Part I and Part II: Time To Steady Plasma Concentration (Tmax,ss) For Zanubrutinib
Time Frame	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	160 mg BID	320 mg QD
Arm/Group Description	Part 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 Participants	33	10
Median (Full Range) [hour]	2.00	2.0

17. Secondary Outcome

Title	Part I: Percentage of BTK Occupied In Peripheral Blood Mononuclear Cells In Participants Who Received Zanubrutinib
Description	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.
Time Frame	DLT 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 Title	Part I: 160 mg BID or 320 mg QD
Arm/Group Description	Safety 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 Participants	13
Mean (Standard Deviation) [Percentage]	96.69 (5.297)

18. Secondary Outcome

Title	Part II: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Description	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.
Time Frame	From 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 Title	Part II: 160 mg BID
Arm/Group Description	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.
Measure Participants	23
Participants with ≥ 1 adverse event	22 200%
Participants with serious adverse events	5 45.5%

Adverse Events

Time Frame	From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
Arm/Group Title	Part I: 160 mg BID		Part I: 320 mg QD		Part II: 160 mg BID
Arm/Group Description	Safety 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 BID		Part I: 320 mg QD		Part II: 160 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)		3/10 (30%)		1/23 (4.3%)
Serious Adverse Events
	Part I: 160 mg BID		Part I: 320 mg QD		Part II: 160 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)		2/10 (20%)		5/23 (21.7%)
Blood and lymphatic system disorders
Anaemia	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Febrile neutropenia	0/11 (0%)		1/10 (10%)		0/23 (0%)
Lymphadenopathy	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Gastrointestinal disorders
Ascites	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
General disorders
Fatigue	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Infections and infestations
Pleural infection	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Pneumonia	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Investigations
Neutrophil count decreased	0/11 (0%)		1/10 (10%)		0/23 (0%)
Platelet count decreased	0/11 (0%)		1/10 (10%)		0/23 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholesterin granuloma of middle ear	1/11 (9.1%)		0/10 (0%)		0/23 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Skin and subcutaneous tissue disorders
Toxic epidermal necrolysis	1/11 (9.1%)		0/10 (0%)		0/23 (0%)
Surgical and medical procedures
Abortion induced	0/11 (0%)		0/10 (0%)		1/23 (4.3%)
Other (Not Including Serious) Adverse Events
	Part I: 160 mg BID		Part I: 320 mg QD		Part II: 160 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/11 (100%)		10/10 (100%)		22/23 (95.7%)
Blood and lymphatic system disorders
Anaemia	4/11 (36.4%)		4/10 (40%)		8/23 (34.8%)
Neutropenia	3/11 (27.3%)		1/10 (10%)		2/23 (8.7%)
Platelet dysfunction	3/11 (27.3%)		1/10 (10%)		2/23 (8.7%)
Hypofibrinogenaemia	1/11 (9.1%)		1/10 (10%)		2/23 (8.7%)
Thrombocytopenia	1/11 (9.1%)		1/10 (10%)		1/23 (4.3%)
Leukopenia	1/11 (9.1%)		0/10 (0%)		1/23 (4.3%)
Gastrointestinal disorders
Constipation	1/11 (9.1%)		1/10 (10%)		3/23 (13%)
Diarrhoea	2/11 (18.2%)		1/10 (10%)		0/23 (0%)
Abdominal pain	0/11 (0%)		0/10 (0%)		2/23 (8.7%)
Abdominal pain upper	0/11 (0%)		1/10 (10%)		1/23 (4.3%)
Mouth ulceration	0/11 (0%)		2/10 (20%)		0/23 (0%)
Nausea	0/11 (0%)		0/10 (0%)		2/23 (8.7%)
Stomatitis	2/11 (18.2%)		0/10 (0%)		0/23 (0%)
General disorders
Pyrexia	1/11 (9.1%)		3/10 (30%)		1/23 (4.3%)
Asthenia	1/11 (9.1%)		1/10 (10%)		0/23 (0%)
Fatigue	2/11 (18.2%)		0/10 (0%)		0/23 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/11 (9.1%)		2/10 (20%)		1/23 (4.3%)
Infections and infestations
Upper respiratory tract infection	5/11 (45.5%)		5/10 (50%)		5/23 (21.7%)
Pneumonia	3/11 (27.3%)		3/10 (30%)		3/23 (13%)
Nasopharyngitis	5/11 (45.5%)		1/10 (10%)		0/23 (0%)
Urinary tract infection	0/11 (0%)		1/10 (10%)		3/23 (13%)
Pharyngitis	0/11 (0%)		2/10 (20%)		1/23 (4.3%)
Gingivitis	0/11 (0%)		1/10 (10%)		1/23 (4.3%)
Investigations
Neutrophil count decreased	8/11 (72.7%)		7/10 (70%)		9/23 (39.1%)
White blood cell count decreased	3/11 (27.3%)		3/10 (30%)		9/23 (39.1%)
Platelet count decreased	4/11 (36.4%)		2/10 (20%)		4/23 (17.4%)
Weight increased	2/11 (18.2%)		3/10 (30%)		3/23 (13%)
Alanine aminotransferase increased	2/11 (18.2%)		2/10 (20%)		0/23 (0%)
Aspartate aminotransferase increased	1/11 (9.1%)		2/10 (20%)		1/23 (4.3%)
Blood creatinine increased	0/11 (0%)		2/10 (20%)		2/23 (8.7%)
Weight decreased	0/11 (0%)		1/10 (10%)		3/23 (13%)
White blood cells urine positive	1/11 (9.1%)		1/10 (10%)		2/23 (8.7%)
Blood alkaline phosphatase increased	0/11 (0%)		1/10 (10%)		2/23 (8.7%)
Blood lactate dehydrogenase increased	2/11 (18.2%)		1/10 (10%)		0/23 (0%)
Blood urine present	0/11 (0%)		1/10 (10%)		2/23 (8.7%)
White blood cell count increased	0/11 (0%)		1/10 (10%)		2/23 (8.7%)
Blood fibrinogen decreased	2/11 (18.2%)		0/10 (0%)		0/23 (0%)
Blood potassium decreased	1/11 (9.1%)		0/10 (0%)		1/23 (4.3%)
Electrocardiogram QT prolonged	1/11 (9.1%)		1/10 (10%)		0/23 (0%)
Gamma-glutamyltransferase increased	1/11 (9.1%)		1/10 (10%)		0/23 (0%)
Haemoglobin decreased	1/11 (9.1%)		0/10 (0%)		1/23 (4.3%)
Lymphocyte count increased	0/11 (0%)		2/10 (20%)		0/23 (0%)
Metabolism and nutrition disorders
Hyperuricaemia	2/11 (18.2%)		3/10 (30%)		5/23 (21.7%)
Hypercholesterolaemia	1/11 (9.1%)		1/10 (10%)		3/23 (13%)
Hypertriglyceridaemia	1/11 (9.1%)		2/10 (20%)		2/23 (8.7%)
Hyperglycaemia	1/11 (9.1%)		1/10 (10%)		1/23 (4.3%)
Hypoalbuminaemia	1/11 (9.1%)		0/10 (0%)		1/23 (4.3%)
Hypocalcaemia	1/11 (9.1%)		1/10 (10%)		0/23 (0%)
Hypokalaemia	1/11 (9.1%)		0/10 (0%)		1/23 (4.3%)
Psychiatric disorders
Insomnia	1/11 (9.1%)		1/10 (10%)		0/23 (0%)
Renal and urinary disorders
Haematuria	4/11 (36.4%)		3/10 (30%)		2/23 (8.7%)
Haemoglobinuria	2/11 (18.2%)		1/10 (10%)		3/23 (13%)
Proteinuria	2/11 (18.2%)		1/10 (10%)		2/23 (8.7%)
Leukocyturia	0/11 (0%)		1/10 (10%)		1/23 (4.3%)
Respiratory, thoracic and mediastinal disorders
Cough	3/11 (27.3%)		3/10 (30%)		2/23 (8.7%)
Dyspnoea	1/11 (9.1%)		0/10 (0%)		1/23 (4.3%)
Laryngeal pain	0/11 (0%)		2/10 (20%)		0/23 (0%)
Oropharyngeal pain	1/11 (9.1%)		1/10 (10%)		0/23 (0%)
Skin and subcutaneous tissue disorders
Rash	3/11 (27.3%)		2/10 (20%)		5/23 (21.7%)
Purpura	2/11 (18.2%)		2/10 (20%)		1/23 (4.3%)
Rash maculo-papular	2/11 (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.