Trial Outcomes & Findings for A Study to Investigate Zanubrutinib in Chinese Participants With B-cell Lymphoma (NCT NCT03189524)
NCT ID: NCT03189524
Last Updated: 2024-12-27
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
44 participants
Primary outcome timeframe
Up to 4 years and 1 month
Results posted on
2024-12-27
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 milestones
| Measure |
Part I: 160 mg BID
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.
|
Part I: 320 mg QD
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.
|
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).
|
|---|---|---|---|
|
Overall Study
STARTED
|
11
|
10
|
23
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
11
|
10
|
23
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
11
|
10
|
23
|
Reasons for withdrawal
| Measure |
Part I: 160 mg BID
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.
|
Part I: 320 mg QD
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.
|
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).
|
|---|---|---|---|
|
Overall Study
Study terminated by Sponsor after final analysis and all remaining participants transferred to LTE
|
7
|
5
|
11
|
|
Overall Study
Death
|
2
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
8
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
3
|
|
Overall Study
Progressive Disease
|
0
|
2
|
0
|
Baseline Characteristics
A Study to Investigate Zanubrutinib in Chinese Participants With B-cell Lymphoma
Baseline characteristics by cohort
| Measure |
Part I: 160 mg BID
n=11 Participants
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.
|
Part I: 320 mg QD
n=10 Participants
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.
|
Part II: 160 mg BID
n=23 Participants
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
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
51.9 years
STANDARD_DEVIATION 10.65 • n=5 Participants
|
52.1 years
STANDARD_DEVIATION 10.57 • n=7 Participants
|
48.4 years
STANDARD_DEVIATION 11.85 • n=5 Participants
|
50.1 years
STANDARD_DEVIATION 11.18 • n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
44 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)Population: 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).
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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=11 Participants
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.
|
Part I: 320 mg QD
n=10 Participants
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.
|
|---|---|---|
|
Part I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Participants with ≥ 1 adverse event
|
11 Participants
|
10 Participants
|
|
Part I: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Participants with serious adverse events
|
2 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: Up to 4 years and 1 monthPopulation: 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).
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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=23 Participants
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.
|
Part I: 320 mg QD
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.
|
|---|---|---|
|
Part II: Overall Response Rate (ORR) Of Zanubrutinib In Participants With FL And MZL
|
30.4 Percentage of Participants
Interval 13.2 to 52.9
|
—
|
PRIMARY outcome
Timeframe: Up to 4 years and 1 monthPopulation: 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).
CRR was defined as the percentage of participants who achieved CR as the best overall response.
Outcome measures
| Measure |
Part I: 160 mg BID
n=23 Participants
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.
|
Part I: 320 mg QD
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.
|
|---|---|---|
|
Part II: Complete Response Rate (CRR) Of Zanubrutinib In Participants With FL And MZL
|
13 Percentage of Participants
Interval 2.8 to 33.6
|
—
|
PRIMARY outcome
Timeframe: Up to 4 years and 1 monthPopulation: 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).
PRR was defined as the percentage of participants who achieved PR or higher as the best overall response.
Outcome measures
| Measure |
Part I: 160 mg BID
n=23 Participants
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.
|
Part I: 320 mg QD
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.
|
|---|---|---|
|
Part II: Partial Response Rate (PRR) Of Zanubrutinib In Participants With FL And MZL
|
30.4 Percentage of Participants
Interval 13.2 to 52.9
|
—
|
PRIMARY outcome
Timeframe: Up to 4 years and 1 monthPopulation: 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).
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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=23 Participants
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.
|
Part I: 320 mg QD
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.
|
|---|---|---|
|
Part II: Duration of Response (DOR) Of Zanubrutinib In Participants With FL And MZL
|
11.2 Months
Interval 2.8 to
NA = Not Estimable due to insufficient number of participants with events
|
—
|
PRIMARY outcome
Timeframe: Up to 4 years and 1 monthPopulation: 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).
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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=23 Participants
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.
|
Part I: 320 mg QD
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.
|
|---|---|---|
|
Part II: Progression Free Survival (PFS) Of Zanubrutinib In Participants With FL And MZL
|
5.5 Months
Interval 4.6 to 16.4
|
—
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=34 Participants
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.
|
Part I: 320 mg QD
n=10 Participants
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.
|
|---|---|---|
|
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 nanogram/milliliter*hour
Standard Deviation 619.6
|
1404 nanogram/milliliter*hour
Standard Deviation 560.7
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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
Outcome measures
| Measure |
Part I: 160 mg BID
n=32 Participants
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.
|
Part I: 320 mg QD
n=9 Participants
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.
|
|---|---|---|
|
Part I and Part II: Area Under The Plasma Concentration-time Curve Zero To Infinity (AUC0-inf) For Single-dose Zanubrutinib
|
1025 nanogram/milliliter*hour
Standard Deviation 633.5
|
1537 nanogram/milliliter*hour
Standard Deviation 519.0
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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
Outcome measures
| Measure |
Part I: 160 mg BID
n=34 Participants
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.
|
Part I: 320 mg QD
n=10 Participants
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.
|
|---|---|---|
|
Part I And Part II: Maximum Plasma Concentration (Cmax) For Single-dose Zanubrutinib
|
319 nanogram/milliliter
Standard Deviation 217
|
409 nanogram/milliliter
Standard Deviation 149
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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
Outcome measures
| Measure |
Part I: 160 mg BID
n=34 Participants
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.
|
Part I: 320 mg QD
n=10 Participants
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.
|
|---|---|---|
|
Part I and Part II: Time To Maximum Plasma Concentration (Tmax) For Single-dose Zanubrutinib
|
2.00 hour
Interval 0.42 to 5.98
|
2.50 hour
Interval 1.0 to 4.0
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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
Outcome measures
| Measure |
Part I: 160 mg BID
n=32 Participants
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.
|
Part I: 320 mg QD
n=9 Participants
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.
|
|---|---|---|
|
Part I and Part II: Apparent Terminal Half Life (t1/2) For Single-dose Zanubrutinib
|
2.27 hour
Standard Deviation 1.21
|
3.43 hour
Standard Deviation 2.23
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=32 Participants
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.
|
Part I: 320 mg QD
n=9 Participants
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.
|
|---|---|---|
|
Part I and Part II: Apparent Plasma Clearance (CL/F) For Single-dose Zanubrutinib
|
251 liter/hour
Standard Deviation 194
|
235 liter/hour
Standard Deviation 93.7
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=32 Participants
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.
|
Part I: 320 mg QD
n=9 Participants
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.
|
|---|---|---|
|
Part I and Part II: Terminal Apparent Volume Of Distribution (Vz/F) For Single-dose Zanubrutinib
|
713 liter
Standard Deviation 512
|
1120 liter
Standard Deviation 738
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=33 Participants
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.
|
Part I: 320 mg QD
n=8 Participants
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.
|
|---|---|---|
|
Part I and Part II: Area Under The Plasma Concentration-time Curve For Steady State (AUCss) Zanubrutinib
|
738.3 nanogram/milliliter*hour
Standard Deviation 425.2
|
1277 nanogram/milliliter*hour
Standard Deviation 607.4
|
SECONDARY outcome
Timeframe: 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-dosePopulation: 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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=33 Participants
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.
|
Part I: 320 mg QD
n=10 Participants
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.
|
|---|---|---|
|
Part I and Part II: Maximum Plasma Concentration At Steady State (Cmax,ss) For Zanubrutinib
|
257 nanogram/milliliter
Standard Deviation 147
|
389 nanogram/milliliter
Standard Deviation 185
|
SECONDARY outcome
Timeframe: 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-doseOutcome measures
| Measure |
Part I: 160 mg BID
n=33 Participants
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.
|
Part I: 320 mg QD
n=10 Participants
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.
|
|---|---|---|
|
Part I and Part II: Time To Steady Plasma Concentration (Tmax,ss) For Zanubrutinib
|
2.00 hour
Interval 0.43 to 2.93
|
2.0 hour
Interval 1.0 to 3.27
|
SECONDARY outcome
Timeframe: DLT Period: Days 1 and 2 of Week 1 and Day 1 of Week 2Population: 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.
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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=13 Participants
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.
|
Part I: 320 mg QD
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.
|
|---|---|---|
|
Part I: Percentage of BTK Occupied In Peripheral Blood Mononuclear Cells In Participants Who Received Zanubrutinib
|
96.69 Percentage
Standard Deviation 5.297
|
—
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Part I: 160 mg BID
n=23 Participants
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.
|
Part I: 320 mg QD
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.
|
|---|---|---|
|
Part II: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Participants with ≥ 1 adverse event
|
22 Participants
|
—
|
|
Part II: Number Of Participants Experiencing Treatment-emergent Adverse Events And Treatment-emergent Serious Adverse Events
Participants with serious adverse events
|
5 Participants
|
—
|
Adverse Events
Part I: 160 mg BID
Serious events: 2 serious events
Other events: 11 other events
Deaths: 2 deaths
Part I: 320 mg QD
Serious events: 2 serious events
Other events: 10 other events
Deaths: 3 deaths
Part II: 160 mg BID
Serious events: 5 serious events
Other events: 22 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Part I: 160 mg BID
n=11 participants at risk
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.
|
Part I: 320 mg QD
n=10 participants at risk
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.
|
Part II: 160 mg BID
n=23 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Platelet count decreased
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
General disorders
Fatigue
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Infections and infestations
Pleural infection
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholesterin granuloma of middle ear
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Skin and subcutaneous tissue disorders
Toxic epidermal necrolysis
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Surgical and medical procedures
Abortion induced
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
Other adverse events
| Measure |
Part I: 160 mg BID
n=11 participants at risk
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.
|
Part I: 320 mg QD
n=10 participants at risk
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.
|
Part II: 160 mg BID
n=23 participants at risk
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.
|
|---|---|---|---|
|
Investigations
Neutrophil count decreased
|
72.7%
8/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
70.0%
7/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
39.1%
9/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
White blood cell count decreased
|
27.3%
3/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
30.0%
3/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
39.1%
9/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Platelet count decreased
|
36.4%
4/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
17.4%
4/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Weight increased
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
30.0%
3/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
13.0%
3/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Alanine aminotransferase increased
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Aspartate aminotransferase increased
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Blood creatinine increased
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Weight decreased
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
13.0%
3/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
White blood cells urine positive
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Blood lactate dehydrogenase increased
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Blood urine present
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
White blood cell count increased
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Blood fibrinogen decreased
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Blood potassium decreased
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Electrocardiogram QT prolonged
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Gamma-glutamyltransferase increased
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Haemoglobin decreased
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Investigations
Lymphocyte count increased
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Infections and infestations
Upper respiratory tract infection
|
45.5%
5/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
50.0%
5/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
21.7%
5/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Infections and infestations
Pneumonia
|
27.3%
3/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
30.0%
3/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
13.0%
3/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Infections and infestations
Nasopharyngitis
|
45.5%
5/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
13.0%
3/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Infections and infestations
Gingivitis
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Blood and lymphatic system disorders
Anaemia
|
36.4%
4/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
40.0%
4/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
34.8%
8/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Blood and lymphatic system disorders
Neutropenia
|
27.3%
3/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Blood and lymphatic system disorders
Platelet dysfunction
|
27.3%
3/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Blood and lymphatic system disorders
Hypofibrinogenaemia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Blood and lymphatic system disorders
Leukopenia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Skin and subcutaneous tissue disorders
Rash
|
27.3%
3/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
21.7%
5/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Skin and subcutaneous tissue disorders
Purpura
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
30.0%
3/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
30.0%
3/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
21.7%
5/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
13.0%
3/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
27.3%
3/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
30.0%
3/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal pain
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
13.0%
3/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Gastrointestinal disorders
Diarrhoea
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Gastrointestinal disorders
Stomatitis
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Renal and urinary disorders
Haematuria
|
36.4%
4/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
30.0%
3/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Renal and urinary disorders
Haemoglobinuria
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
13.0%
3/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Renal and urinary disorders
Proteinuria
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
8.7%
2/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Renal and urinary disorders
Leukocyturia
|
0.00%
0/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
General disorders
Pyrexia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
30.0%
3/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
General disorders
Asthenia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
General disorders
Fatigue
|
18.2%
2/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
20.0%
2/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
4.3%
1/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
|
Psychiatric disorders
Insomnia
|
9.1%
1/11 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
10.0%
1/10 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
0.00%
0/23 • From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER