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| ID | Type | Description | Link |
|---|---|---|---|
| CTR20160204 | Registry Identifier | Center for drug evaluation, CFDA |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I: 160 mg BID | Experimental | 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). |
|
| Part I: 320 mg QD | Experimental | 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. |
|
| Part II: 160 mg BID | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zanubrutinib | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Part I and Part II: Area Under The Plasma Concentration-time Curve From Zero To The Last Measurable Concentration (AUClast) For Single-dose Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose | |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Other protocol defined Inclusion/Exclusion criteria may have applied.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | BeiGene | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Beijing | Beijing Municipality | 100142 | China | ||
| Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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 | ||
| 38502198 | Derived | Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641. | |
| 35900694 |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part I: 160 mg BID | 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. |
| BG001 | Part I: 320 mg QD |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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). | Posted | Count of Participants | Participants | From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month) |
From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part I: 160 mg BID | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | BeiGene | +1-877-828-5568 | clinicaltrials@beigene.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 6, 2017 | Aug 18, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 1, 2017 | Aug 18, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000629551 | zanubrutinib |
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|
|
| 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. | 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. | Up to 4 years and 1 month |
| Part I and Part II: Area Under The Plasma Concentration-time Curve Zero To Infinity (AUC0-inf) For Single-dose Zanubrutinib |
| Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| Part I And Part II: Maximum Plasma Concentration (Cmax) For Single-dose Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| Part I and Part II: Time To Maximum Plasma Concentration (Tmax) For Single-dose Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| Part I and Part II: Apparent Terminal Half Life (t1/2) For Single-dose Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| Part I and Part II: Apparent Plasma Clearance (CL/F) For Single-dose Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| Part I and Part II: Terminal Apparent Volume Of Distribution (Vz/F) For Single-dose Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| Part I and Part II: Area Under The Plasma Concentration-time Curve For Steady State (AUCss) Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| Part I and Part II: Maximum Plasma Concentration At Steady State (Cmax,ss) For Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| Part I and Part II: Time To Steady Plasma Concentration (Tmax,ss) For Zanubrutinib | Part 1 and 2 : Week 1 day1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, 12 and 24 hours, and Week 2-day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6 (part2 only), 8, and 12 hours (part2 only), and Week 5 and Week 9 Day 1 Pre-dose |
| 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. | 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. | From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month) |
| Wuhan |
| Hubei |
| 430030 |
| China |
| Jiangsu Province Hospital | Nanjing | Jiangsu | 210029 | China |
| Institute of Hematology and Hospital of Blood Disease | Tianjin | Tianjin Municipality | 300020 | China |
| Derived |
| 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. |
| 35383885 | Derived | 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. |
| Lost to Follow-up |
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| Withdrawal by Subject |
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| Progressive Disease |
|
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. |
| BG002 | 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 FL or MZL. |
| BG003 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Primary | 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. | 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). | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to 4 years and 1 month |
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| Primary | 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. | 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). | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to 4 years and 1 month |
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| Primary | 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. | 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). | Posted | Number | 95% Confidence Interval | Percentage of Participants | Up to 4 years and 1 month |
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| Primary | 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. | 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). | Posted | Median | 95% Confidence Interval | Months | Up to 4 years and 1 month |
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| Primary | 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. | 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). | Posted | Median | 95% Confidence Interval | Months | Up to 4 years and 1 month |
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| Secondary | Part I and Part II: Area Under The Plasma Concentration-time Curve From Zero To The Last Measurable Concentration (AUClast) For Single-dose Zanubrutinib | 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. | Posted | Mean | Standard Deviation | nanogram/milliliter*hour | 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 |
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| Secondary | Part I and Part II: Area Under The Plasma Concentration-time Curve Zero To Infinity (AUC0-inf) For Single-dose Zanubrutinib | 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 | Posted | Mean | Standard Deviation | nanogram/milliliter*hour | 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 |
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| Secondary | Part I And Part II: Maximum Plasma Concentration (Cmax) For Single-dose Zanubrutinib | 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 | Posted | Mean | Standard Deviation | nanogram/milliliter | 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 |
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| Secondary | Part I and Part II: Time To Maximum Plasma Concentration (Tmax) For Single-dose Zanubrutinib | 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 | Posted | Median | Full Range | hour | 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 |
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| Secondary | Part I and Part II: Apparent Terminal Half Life (t1/2) For Single-dose Zanubrutinib | 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 | Posted | Mean | Standard Deviation | hour | 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 |
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| Secondary | Part I and Part II: Apparent Plasma Clearance (CL/F) For Single-dose Zanubrutinib | 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. | Posted | Mean | Standard Deviation | liter/hour | 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 |
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| Secondary | Part I and Part II: Terminal Apparent Volume Of Distribution (Vz/F) For Single-dose Zanubrutinib | 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. | Posted | Mean | Standard Deviation | liter | 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 |
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| Secondary | Part I and Part II: Area Under The Plasma Concentration-time Curve For Steady State (AUCss) Zanubrutinib | 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. | Posted | Mean | Standard Deviation | nanogram/milliliter*hour | 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 |
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| Secondary | Part I and Part II: Maximum Plasma Concentration At Steady State (Cmax,ss) For Zanubrutinib | 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. | Posted | Mean | Standard Deviation | nanogram/milliliter | 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 |
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| Secondary | Part I and Part II: Time To Steady Plasma Concentration (Tmax,ss) For Zanubrutinib | Posted | Median | Full Range | hour | 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 |
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| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | Percentage | DLT Period: Days 1 and 2 of Week 1 and Day 1 of Week 2 |
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| Secondary | 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. | Posted | Count of Participants | Participants | From the date of informed consent until 30 +/- 7 days after treatment discontinuation (up to 4 years and 1 month) |
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| 2 |
| 11 |
| 2 |
| 11 |
| 11 |
| 11 |
| EG001 | 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. | 3 | 10 | 2 | 10 | 10 | 10 |
| EG002 | 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 FL or MZL. | 1 | 23 | 5 | 23 | 22 | 23 |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Pleural infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Cholesterin granuloma of middle ear | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Toxic epidermal necrolysis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Abortion induced | Surgical and medical procedures | MedDRA 23.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| White blood cells urine positive | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood lactate dehydrogenase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood urine present | Investigations | MedDRA 23.0 | Systematic Assessment |
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| White blood cell count increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood fibrinogen decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Blood potassium decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Lymphocyte count increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Gingivitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Platelet dysfunction | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypofibrinogenaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Purpura | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Laryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
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| Haemoglobinuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
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| Leukocyturia | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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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.
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |