CompletedNCT03189524Updated Dec 27, 2024Results posted

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

A Phase 1 interventional study of Zanubrutinib in B-cell Lymphoma, sponsored by BeiGene. Completed at 4 sites in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-12-27.

Sponsored by BeiGene · Phase 1, Interventional, and Treatment

From the registry’s dates

Registered 11 months after the study started (first participant enrolled Jul 2016, registered Jun 2017).

Phase: Phase 1
Study type: Interventional
Enrollment: 44
Allocation: Non-randomized
Ages: 18 Years to 75 Years
Sex: All

Study 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.

Conditions studied

B-cell Lymphoma

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In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 44 is close to the median of 40 across 4,508 interventional studies indexed under Lymphoma.

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Lead sponsor

BeiGene is the lead sponsor of 122 studies on the registry; 3 are open to participants now.

Of its 52 completed or terminated interventional studies of FDA-regulated products, 31 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 44 participants (actual)

Study arms

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
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
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

Interventions

DrugZanubrutinib
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.
Also known as: BGB-3111

What researchers measure

Primary outcomes

Part I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
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)
Part II: Overall Response Rate (ORR) Of Zanubrutinib In Participants With FL And MZL
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
Part II: Complete Response Rate (CRR) Of Zanubrutinib In Participants With FL And MZL
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
Part II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL
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
Part II: Duration of Response (DOR) Of Zanubrutinib In Participants With FL And MZL
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
Part II: Progression Free Survival (PFS) Of Zanubrutinib In Participants With FL And MZL
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

Secondary outcomes

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
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
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
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
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
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
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
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
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
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
Part I: Percentage of BTK Occupied In Peripheral Blood Mononuclear Cells In Participants Who Received Zanubrutinib
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
Part II: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
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)

Results

Posted Oct 22, 2021

Participant flow

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.

Participant flow — Overall Study
Milestone	Part I: 160 mg BID	Part I: 320 mg QD	Part II: 160 mg BID
Started	11	10	23
Received at least 1 dose of study drug	11	10	23
Completed	0	0	0
Not completed	11	10	23
Withdrew: Study terminated by sponsor after final analysis and all remaining participants transferred to lte	7	5	11
Withdrew: Death	2	2	1
Withdrew: Lost to follow-up	1	0	8
Withdrew: Withdrawal by subject	1	1	3
Withdrew: Progressive disease	0	2	0

Outcome measures

PrimaryPart I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events

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)
Reported as:: Count of participants · Participants

Part I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Participants	Part I: 160 mg BID	Part I: 320 mg QD
Participants with ≥ 1 adverse event	11	10
Participants with serious adverse events	2	2

PrimaryPart II: Overall Response Rate (ORR) Of Zanubrutinib In Participants With FL And MZL

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
Reported as:: Number · Percentage of Participants

Part II: Overall Response Rate (ORR) Of Zanubrutinib In Participants With FL And MZL
Percentage of Participants	Part II: 160 mg BID
Part II: Overall Response Rate (ORR) Of Zanubrutinib In Participants With FL And MZL	30.4 (13.2 to 52.9)

PrimaryPart II: Complete Response Rate (CRR) Of Zanubrutinib In Participants With FL And MZL

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
Reported as:: Number · Percentage of Participants

Part II: Complete Response Rate (CRR) Of Zanubrutinib In Participants With FL And MZL
Percentage of Participants	Part II: 160 mg BID
Part II: Complete Response Rate (CRR) Of Zanubrutinib In Participants With FL And MZL	13 (2.8 to 33.6)

PrimaryPart II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL

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
Reported as:: Number · Percentage of Participants

Part II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL
Percentage of Participants	Part II: 160 mg BID
Part II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL	30.4 (13.2 to 52.9)

PrimaryPart II: Duration of Response (DOR) Of Zanubrutinib In Participants With FL And MZL

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
Reported as:: Median · Months

Part II: Duration of Response (DOR) Of Zanubrutinib In Participants With FL And MZL
Months	Part II: 160 mg BID
Part II: Duration of Response (DOR) Of Zanubrutinib In Participants With FL And MZL	11.2 (2.8 to NA)

PrimaryPart II: Progression Free Survival (PFS) Of Zanubrutinib In Participants With FL And MZL

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
Reported as:: Median · Months

Part II: Progression Free Survival (PFS) Of Zanubrutinib In Participants With FL And MZL
Months	Part II: 160 mg BID
Part II: Progression Free Survival (PFS) Of Zanubrutinib In Participants With FL And MZL	5.5 (4.6 to 16.4)

SecondaryPart 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
Reported as:: Mean · nanogram/milliliter*hour

Part I and Part II: Area Under The Plasma Concentration-time Curve From Zero To The Last Measurable Concentration (AUClast) For Single-dose Zanubrutinib
nanogram/milliliter*hour	160 mg BID	320 mg QD
Part I and Part II: Area Under The Plasma Concentration-time Curve From Zero To The Last Measurable Concentration (AUClast) For Single-dose Zanubrutinib	981.6 ± 619.6	1404 ± 560.7

SecondaryPart 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
Reported as:: Mean · nanogram/milliliter*hour

Part I and Part II: Area Under The Plasma Concentration-time Curve Zero To Infinity (AUC0-inf) For Single-dose Zanubrutinib
nanogram/milliliter*hour	160 mg BID	320 mg QD
Part I and Part II: Area Under The Plasma Concentration-time Curve Zero To Infinity (AUC0-inf) For Single-dose Zanubrutinib	1025 ± 633.5	1537 ± 519.0

SecondaryPart 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
Reported as:: Mean · nanogram/milliliter

Part I And Part II: Maximum Plasma Concentration (Cmax) For Single-dose Zanubrutinib
nanogram/milliliter	160 mg BID	320 mg QD
Part I And Part II: Maximum Plasma Concentration (Cmax) For Single-dose Zanubrutinib	319 ± 217	409 ± 149

SecondaryPart 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
Reported as:: Median · hour

Part I and Part II: Time To Maximum Plasma Concentration (Tmax) For Single-dose Zanubrutinib
hour	160 mg BID	320 mg QD
Part I and Part II: Time To Maximum Plasma Concentration (Tmax) For Single-dose Zanubrutinib	2.00 (0.42 to 5.98)	2.50 (1.00 to 4.00)

SecondaryPart 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
Reported as:: Mean · hour

Part I and Part II: Apparent Terminal Half Life (t1/2) For Single-dose Zanubrutinib
hour	160 mg BID	320 mg QD
Part I and Part II: Apparent Terminal Half Life (t1/2) For Single-dose Zanubrutinib	2.27 ± 1.21	3.43 ± 2.23

SecondaryPart 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
Reported as:: Mean · liter/hour

Part I and Part II: Apparent Plasma Clearance (CL/F) For Single-dose Zanubrutinib
liter/hour	160 mg BID	320 mg QD
Part I and Part II: Apparent Plasma Clearance (CL/F) For Single-dose Zanubrutinib	251 ± 194	235 ± 93.7

SecondaryPart 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
Reported as:: Mean · liter

Part I and Part II: Terminal Apparent Volume Of Distribution (Vz/F) For Single-dose Zanubrutinib
liter	160 mg	320 mg QD
Part I and Part II: Terminal Apparent Volume Of Distribution (Vz/F) For Single-dose Zanubrutinib	713 ± 512	1120 ± 738

SecondaryPart 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
Reported as:: Mean · nanogram/milliliter*hour

Part I and Part II: Area Under The Plasma Concentration-time Curve For Steady State (AUCss) Zanubrutinib
nanogram/milliliter*hour	160 mg BID	320 mg QD
Part I and Part II: Area Under The Plasma Concentration-time Curve For Steady State (AUCss) Zanubrutinib	738.3 ± 425.2	1277 ± 607.4

SecondaryPart 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
Reported as:: Mean · nanogram/milliliter

Part I and Part II: Maximum Plasma Concentration At Steady State (Cmax,ss) For Zanubrutinib
nanogram/milliliter	160 mg BID	320 mg QD
Part I and Part II: Maximum Plasma Concentration At Steady State (Cmax,ss) For Zanubrutinib	257 ± 147	389 ± 185

SecondaryPart 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
Reported as:: Median · hour

Part I and Part II: Time To Steady Plasma Concentration (Tmax,ss) For Zanubrutinib
hour	160 mg BID	320 mg QD
Part I and Part II: Time To Steady Plasma Concentration (Tmax,ss) For Zanubrutinib	2.00 (0.43 to 2.93)	2.0 (1.00 to 3.27)

SecondaryPart I: Percentage of BTK Occupied In Peripheral Blood Mononuclear Cells In Participants Who Received Zanubrutinib

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
Reported as:: Mean · Percentage

Part I: Percentage of BTK Occupied In Peripheral Blood Mononuclear Cells In Participants Who Received Zanubrutinib
Percentage	Part I: 160 mg BID or 320 mg QD
Part I: Percentage of BTK Occupied In Peripheral Blood Mononuclear Cells In Participants Who Received Zanubrutinib	96.69 ± 5.297

SecondaryPart II: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events

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)
Reported as:: Count of participants · Participants

Part II: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Participants	Part II: 160 mg BID
Participants with ≥ 1 adverse event	22
Participants with serious adverse events	5

Adverse events

Collected over From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month). Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part I: 160 mg BID	2/11 (18.2%)	2/11 (18.2%)	11/11 (100%)
Part I: 320 mg QD	3/10 (30%)	2/10 (20%)	10/10 (100%)
Part II: 160 mg BID	1/23 (4.3%)	5/23 (21.7%)	22/23 (95.7%)

Most frequent serious events

Showing 10 of 15

Most frequent serious events
Event	Part I: 160 mg BID	Part I: 320 mg QD	Part II: 160 mg BID
Febrile neutropeniaBlood and lymphatic system disorders	0/11	1/10	0/23
Neutrophil count decreasedInvestigations	0/11	1/10	0/23
Platelet count decreasedInvestigations	0/11	1/10	0/23
Cholesterin granuloma of middle earNeoplasms benign, malignant and unspecified (incl cysts and polyps)	1/11	0/10	0/23
Toxic epidermal necrolysisSkin and subcutaneous tissue disorders	1/11	0/10	0/23
AnaemiaBlood and lymphatic system disorders	0/11	0/10	1/23
LymphadenopathyBlood and lymphatic system disorders	0/11	0/10	1/23
AscitesGastrointestinal disorders	0/11	0/10	1/23
FatigueGeneral disorders	0/11	0/10	1/23
Pleural infectionInfections and infestations	0/11	0/10	1/23

Most frequent other events

Showing 10 of 61

Most frequent other events
Event	Part I: 160 mg BID	Part I: 320 mg QD	Part II: 160 mg BID
Neutrophil count decreasedInvestigations	8/11	7/10	9/23
Upper respiratory tract infectionInfections and infestations	5/11	5/10	5/23
NasopharyngitisInfections and infestations	5/11	1/10	0/23
AnaemiaBlood and lymphatic system disorders	4/11	4/10	8/23
White blood cell count decreasedInvestigations	3/11	3/10	9/23
Platelet count decreasedInvestigations	4/11	2/10	4/23
HaematuriaRenal and urinary disorders	4/11	3/10	2/23
Weight increasedInvestigations	2/11	3/10	3/23
PneumoniaInfections and infestations	3/11	3/10	3/23
Rash maculo-papularSkin and subcutaneous tissue disorders	2/11	3/10	0/23

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Part I: 160 mg BID	Part I: 320 mg QD	Part II: 160 mg BID	Total
Mean	51.9 ± 10.65	52.1 ± 10.57	48.4 ± 11.85	50.1 ± 11.18

Sex: Female, Male
Sex: Female, Male(Participants)	Part I: 160 mg BID	Part I: 320 mg QD	Part II: 160 mg BID	Total
Female	2	3	15	20
Male	9	7	8	24

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Part I: 160 mg BID	Part I: 320 mg QD	Part II: 160 mg BID	Total
American Indian or Alaska Native	0	0	0	0
Asian	11	10	23	44
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	0	0	0
White	0	0	0	0
More than one race	0	0	0	0
Unknown or Not Reported	0	0	0	0

Study locations

4 sites

Beijing Cancer Hospital
Beijing, Beijing 100142, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei 430030, China
Jiangsu Province Hospital
Nanjing, Jiangsu 210029, China
Institute of Hematology and Hospital of Blood Disease
Tianjin, Tianjin 300020, China

References and documents

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
Xu W, Yang S, Tam CS, Seymour JF, Zhou K, Opat S, Qiu L, Sun M, Wang T, Trotman J, Pan L, Gao S, Zhou J, Zhou D, Zhu J, Song Y, Hu J, Feng R, Huang H, Su D, Shi M, Li J. Zanubrutinib Monotherapy for Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Adv Ther. 2022 Sep;39(9):4250-4265. doi: 10.1007/s12325-022-02238-7. Epub 2022 Jul 28. PubMed 35900694 ↗
Song Y, Sun M, Qi J, Xu W, Zhou J, Li D, Li J, Qiu L, Du C, Guo H, Huang J, Tang Z, Ou Y, Wu B, Yu Y, Zhu J. A two-part, single-arm, multicentre, phase I study of zanubrutinib, a selective Bruton tyrosine kinase inhibitor, in Chinese patients with relapsed/refractory B-cell malignancies. Br J Haematol. 2022 Jul;198(1):62-72. doi: 10.1111/bjh.18162. Epub 2022 Apr 5. PubMed 35383885 ↗

Study documents

Study protocol · Feb 6, 2017
Statistical analysis plan · Nov 1, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 27, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03189524
Lead sponsor: BeiGene
Responsible party: Sponsor
First posted: Jun 16, 2017
Start date: Jul 5, 2016
Primary completion: Aug 26, 2020
Completion: Aug 26, 2020
Results posted: Oct 22, 2021
Last update: Dec 27, 2024

Study contacts

Study Director

principal investigator · BeiGene

View the source record on ClinicalTrials.gov ↗

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