Study of BTK Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)

• Sponsor: BeiGene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03332173
• Collaborator: (none)
• Enrollment: 44
• Locations: 11
• Arm: 1
• Actual Duration (Months): 40.4
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a single-arm, multicenter Phase 2 study in Chinese participants with relapsed or refractory Waldenström's macroglobulinemia who exhibited one or more of the criteria for requiring treatment based on consensus guidelines from the Seventh International Workshop on Waldenström's Macroglobulinemia (IWWM). The study comprised an initial screening phase (up to 28 days), a single-arm treatment phase, and a follow-up phase.

Condition or Disease	Intervention/Treatment	Phase
Waldenström's Macroglobulinemia (WM)	Drug: Zanubrutinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Single-Arm, Open-Label, Multicenter Study of Bruton's Tyrosine Kinase (BTK) Inhibitor BGB-3111 in Chinese Subjects With Relapsed/Refractory Waldenström's Macroglobulinemia (WM)
• Actual Study Start Date: Aug 31, 2017
• Actual Primary Completion Date: May 8, 2019
• Actual Study Completion Date: Jan 11, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zanubrutinib Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity	Drug: Zanubrutinib; Oral administration using 80 mg capsules; Other Names: BGB-3111 Brukinsa

Outcome Measures

Primary Outcome Measures

1. Major Response Rate (MRR) as Assessed by the Independent Review Committee [Up to approximately 1 year and 9 months]

   MRR is defined as the percentage of participants who achieved complete response (CR) + very good partial response (VGPR) + partial response (PR), as assessed by an independent review committee according to modified Owen's criteria

Secondary Outcome Measures

1. Progression Free Survival (PFS) [Up to approximately 1 year and 9 months]

   PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by an independent review committee using modified Owen's criteria

2. PFS: Event-free Rate [Up to approximately 1 year and 9 months]

   Progression/death event-free rates were estimated by Kaplan-Meier method with 95% confidence intervals (CIs) estimated using Greenwood's formula

3. Overall Response Rate (ORR) [Up to approximately 1 year and 9 months]

   ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response, as assessed by an independent review committee using modified Owen's criteria

4. Duration of Major Response (DOMR) [Up to approximately 1 year and 9 months]

   DOMR is defined as the time from the date that the major response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever comes first, as assessed by an independent review committee using modified Owen's criteria

5. DOMR: Event-free Rate [Up to approximately 1 year and 9 months]

   DOMR event-free rates were estimated by Kaplan-Meier method with 95% CIs estimated using Greenwood's formula

6. Number of Participants With Resolution of Treatment-precipitating Symptoms [Up to approximately 1 year and 9 months]

   Number of participants with resolution of treatment-precipitating symptoms, defined as any resolution (from "Yes" at baseline to "No" at any postbaseline point onwards during study) of the indications for initiation of therapy in WM signs and symptoms evaluation.

7. Number of Participants With an Anti-lymphoma Effect [Up to approximately 1 year and 9 months]

   Number of participants with an anti-lymphoma effect, defined as any reduction during the course of study in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or splenomegaly by computed tomography scan as assessed by an independent review committee; lymphadenopathy is defined as any node with longest diameter (LDi) > 1.5 cm and splenomegaly is defined as vertical spleen length > 13 cm

8. Number of Participants With Adverse Events [Up to approximately 3 years and 5 months]

   Number of participants with treatment-emergent adverse events (TEAEs), grade 3 or higher TEAEs, serious adverse events (SAEs), treatment-related adverse events (AEs), adverse events of special interest, and TEAEs leading to study drug discontinuation, dose reduction and treatment interruption

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Clinical and definitive histologic diagnosis of WM, meeting at least one criterion for treatment according to consensus panel criteria from the Seventh IWWM.

2. WM pathology confirmation by central lab prior to study enrollment. Previous pathology report, concurrently with newly generated central lab report to be reviewed to support WM diagnosis.

3. Men and women ≥ 18 years of age.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

5. Previously treated with a minimum of 1 prior line of standard chemotherapy-containing regimen (with completion of ≥ 2 continuous treatment cycles).

6. Documented failure to achieve at least minor response or documented disease progression after response to the most recent treatment regimen.

7. Neutrophils ≥ 0.75 x 10^9/L independent of growth factor support within 7 days of first dose.

8. Platelets ≥ 50 x 10^9/L, independent of growth factor support or transfusion within 7 days of first dose.

9. Hemoglobin ≥80 g/L, independent of erythropoietin (EPO) support or transfusion within 7 days of first dose of study drug.

10. Creatinine clearance of ≥ 30 mL/min (as estimated by the Cockcroft-Gault equation or estimated glomerular filtration rate [eGFR] from the Modification of Diet in Renal Disease [MDRD]).

11. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN).

12. Bilirubin ≤ 2 x ULN (unless documented Gilbert's syndrome).

13. International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x ULN. Participants with lupus anticoagulant or acquired von Willebrand disease due to WM may be enrolled after discussion with the medical monitor.

14. ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥50%.

15. Participants who relapse after autologous stem cell transplant may be enrolled if they are at least 6 months after transplant at screening. To be eligible after transplant, participants should have no active related infections.

16. Females of childbearing potential must agree to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Highly effective forms of birth control can be defined as abstinence, hysterectomy, bilateral oophorectomy with no menstrual bleeding for up to 6 months, intrauterine contraception, hormonal methods such as contraceptive injection, oral contraceptive, etc. Males must have undergone sterilization-vasectomy, or use a barrier method where the female partner uses the effective forms of birth control noted above and must not donate sperm for at least 90 days after last dose of study drug.

17. Life expectancy of > 4 months.

18. Able to provide written informed consent and can understand and comply with the requirements of the study.

Key Exclusion Criteria:

1. Central nervous system (CNS) involvement by WM.

2. Prior exposure to a BTK inhibitor.

3. Evidence of disease transformation.

4. Prior corticosteroids given in excess of prednisone 10 mg/day or its equivalent with antineoplastic intent within 7 days, prior chemotherapy, targeted therapy, or radiation therapy within 3 weeks, antineoplastic therapy with Chinese herbal medicine or antibody based therapies within 4 weeks of the start of study drug.

5. Major surgery within 4 weeks of randomization.

6. Toxicity of ≥ Grade 1 from prior anti-cancer therapy (except for absolute neutrophil count [ANC], platelets, and hemoglobin. For ANC, platelets, and hemoglobin, please follow inclusion criteria #7 [neutrophils], #8 [platelets], and #9 [hemoglobin]).

7. History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.

8. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, uncontrolled hypertension, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification, or history of myocardial infarction within 6 months of screening.

9. QTcF prolongation (defined as a QTc >480 msecs based on Fridericia's formula) or other significant ECG abnormalities including second degree atrioventricular (AV) block Type II, or third degree AV block.

10. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

11. Active infection including infections requiring oral or intravenous anti-microbial therapy.

12. Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C infection (detected positive by polymerase chain reaction [PCR]).

13. Pregnant or lactating women.

14. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study at risk.

15. On medications which are strong CYP3A inhibitors or strong CYP3A inducers.

16. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

17. Has received allogenic hematopoietic stem cell transplantation prior to enrollment.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking Union Medical College Hospital	Beijing	Beijing	China
2	Peking University People's Hospital	Beijing	Beijing	China
3	Guangdong General Hospital	Guangzhou	Guangdong	China
4	Henan Cancer Hospital	Zhengzhou	Henan	China
5	Tongji Hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei	China
6	Jiangsu Province Hospital	Nanjing	Jiangsu	China
7	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China
8	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China
9	West China Hospital, Sichuan University	Chengdu	Sichuan	China
10	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin	China
11	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang	China

Sponsors and Collaborators

• BeiGene

Investigators

• Principal Investigator: Study Director, BeiGene

Study Documents (Full-Text)

• Study Protocol - Mar 30, 2018
• Statistical Analysis Plan - May 15, 2019

More Information

Publications

• An G, Zhou D, Cheng S, Zhou K, Li J, Zhou J, Xie L, Jin J, Zhong L, Yan L, Guo H, Du C, Zhong J, Yu Y, Wu B, Qiu L. A Phase II Trial of the Bruton Tyrosine-Kinase Inhibitor Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Waldenström Macroglobulinemia. Clin Cancer Res. 2021 Oct 15;27(20):5492-5501. doi: 10.1158/1078-0432.CCR-21-0539. Epub 2021 Jul 12.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT03332173
• Other Study ID Numbers: BGB-3111-210; CTR20170208
• First Posted: Nov 6, 2017
• Last Update Posted: Mar 9, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Waldenstrom Macroglobulinemia; Zanubrutinib

Study Results

Participant Flow

Recruitment Details	This study enrolled participants at 10 study centers in China. The first participant was dosed on 31 August 2017, and the last participant enrolled and received their first dose of zanubrutinib on 08 May 2018. A total of 44 participants were enrolled and all received at least 1 dose of the study drug.
Pre-assignment Detail	The protocol-defined efficacy analyses were performed 12 months after the last patient received the first dose of study drug, with a data cutoff date of 08 May 2019.

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Period Title: Overall Study
STARTED	44
COMPLETED	0
NOT COMPLETED	44

Baseline Characteristics

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Overall Participants	44
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.7 (8.10)
Sex: Female, Male (Count of Participants)
Female	17 38.6%
Male	27 61.4%
Race/Ethnicity, Customized (Count of Participants)
Chinese	44 100%

Outcome Measures

1. Primary Outcome

Title	Major Response Rate (MRR) as Assessed by the Independent Review Committee
Description	MRR is defined as the percentage of participants who achieved complete response (CR) + very good partial response (VGPR) + partial response (PR), as assessed by an independent review committee according to modified Owen's criteria
Time Frame	Up to approximately 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	43
Number (95% Confidence Interval) [Percentage of participants]	69.8 158.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zanubrutinib
	Comments	Zanubrutinib versus historical control estimate of 30%
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value was based on the exact binomial test against the null hypothesis H0: MRR = 0.30 at a significance level of 0.025 (1-sided)
	Method	Exact binomial test
	Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by an independent review committee using modified Owen's criteria
Time Frame	Up to approximately 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	43
Median (95% Confidence Interval) [Months]	NA

3. Secondary Outcome

Title	PFS: Event-free Rate
Description	Progression/death event-free rates were estimated by Kaplan-Meier method with 95% confidence intervals (CIs) estimated using Greenwood's formula
Time Frame	Up to approximately 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	43
6 months	89.8 204.1%
9 months	87.0 197.7%
12 months	77.8 176.8%

4. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	ORR is defined as the percentage of participants with a minor, partial, very good partial, and complete response, as assessed by an independent review committee using modified Owen's criteria
Time Frame	Up to approximately 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	43
Number (95% Confidence Interval) [Percentage of participants]	79.1 179.8%

5. Secondary Outcome

Title	Duration of Major Response (DOMR)
Description	DOMR is defined as the time from the date that the major response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever comes first, as assessed by an independent review committee using modified Owen's criteria
Time Frame	Up to approximately 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	43
Median (95% Confidence Interval) [Months]	NA

6. Secondary Outcome

Title	DOMR: Event-free Rate
Description	DOMR event-free rates were estimated by Kaplan-Meier method with 95% CIs estimated using Greenwood's formula
Time Frame	Up to approximately 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	43
6 months	96.2 218.6%
9 months	87.0 197.7%
12 months	87.0 197.7%

7. Secondary Outcome

Title	Number of Participants With Resolution of Treatment-precipitating Symptoms
Description	Number of participants with resolution of treatment-precipitating symptoms, defined as any resolution (from "Yes" at baseline to "No" at any postbaseline point onwards during study) of the indications for initiation of therapy in WM signs and symptoms evaluation.
Time Frame	Up to approximately 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	43
Count of Participants [Participants]	35 79.5%

8. Secondary Outcome

Title	Number of Participants With an Anti-lymphoma Effect
Description	Number of participants with an anti-lymphoma effect, defined as any reduction during the course of study in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or splenomegaly by computed tomography scan as assessed by an independent review committee; lymphadenopathy is defined as any node with longest diameter (LDi) > 1.5 cm and splenomegaly is defined as vertical spleen length > 13 cm
Time Frame	Up to approximately 1 year and 9 months

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set includes participants with confirmed Waldenström's macroglobulinemia based on central pathologic review among those who received at least one dose of study drug and with a baseline IgM (or M-protein) ≥ 5 g/L

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	43
Count of Participants [Participants]	34 77.3%

9. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Number of participants with treatment-emergent adverse events (TEAEs), grade 3 or higher TEAEs, serious adverse events (SAEs), treatment-related adverse events (AEs), adverse events of special interest, and TEAEs leading to study drug discontinuation, dose reduction and treatment interruption
Time Frame	Up to approximately 3 years and 5 months

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received ≥ 1 dose of study drug

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
Measure Participants	44
At least one TEAE	44 100%
Grade 3 or higher TEAEs	34 77.3%
Serious TEAEs	25 56.8%
Treatment-related TEAEs	41 93.2%
TEAEs of special interest	43 97.7%
TEAEs leading to study drug discontinuation	5 11.4%
TEAEs leading to treatment interruption	17 38.6%
TEAEs leading to dose reduction	1 2.3%

Adverse Events

Time Frame	Up to approximately 3 years and 5 months
Adverse Event Reporting Description	A treatment-emergent adverse event (TEAE) was defined as an adverse event that had an onset or worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days after the last dose of study drug or initiation of new anticancer therapy, whichever occurred first. Worsening of an event to Grade 5 beyond 30 days after the last dose of study drug was also considered a TEAE (if prior to start of new anticancer therapy).
Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg orally twice daily with or without food until progressive disease or intolerable toxicity
All Cause Mortality
	Zanubrutinib
	Affected / at Risk (%)	# Events
Total	7/44 (15.9%)
Serious Adverse Events
	Zanubrutinib
	Affected / at Risk (%)	# Events
Total	25/44 (56.8%)
Blood and lymphatic system disorders
Anaemia	1/44 (2.3%)
Cardiac disorders
Arteriosclerosis coronary artery	1/44 (2.3%)
Coronary artery disease	1/44 (2.3%)
Eye disorders
Cataract	1/44 (2.3%)
Macular degeneration	1/44 (2.3%)
Gastrointestinal disorders
Dysbiosis	1/44 (2.3%)
Upper gastrointestinal haemorrhage	1/44 (2.3%)
General disorders
Death	1/44 (2.3%)
Multiple organ dysfunction syndrome	1/44 (2.3%)
Infections and infestations
Abscess limb	1/44 (2.3%)
Acute hepatitis B	1/44 (2.3%)
Epididymitis	1/44 (2.3%)
Pneumonia	10/44 (22.7%)
Pulmonary mycosis	1/44 (2.3%)
Skin infection	2/44 (4.5%)
Upper respiratory tract infection	3/44 (6.8%)
Injury, poisoning and procedural complications
Fracture	1/44 (2.3%)
Spinal compression fracture	1/44 (2.3%)
Investigations
Platelet count decreased	1/44 (2.3%)
Musculoskeletal and connective tissue disorders
Synovial cyst	1/44 (2.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal cancer	1/44 (2.3%)
Lung neoplasm malignant	1/44 (2.3%)
Waldenstrom's macroglobulinaemia	1/44 (2.3%)
Nervous system disorders
Intracranial mass	1/44 (2.3%)
Post herpetic neuralgia	1/44 (2.3%)
Syncope	1/44 (2.3%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/44 (4.5%)
Vascular disorders
Hypertension	1/44 (2.3%)
Other (Not Including Serious) Adverse Events
	Zanubrutinib
	Affected / at Risk (%)	# Events
Total	44/44 (100%)
Blood and lymphatic system disorders
Anaemia	8/44 (18.2%)
Leukopenia	3/44 (6.8%)
Neutropenia	2/44 (4.5%)
Cardiac disorders
Angina pectoris	2/44 (4.5%)
Eye disorders
Cataract	3/44 (6.8%)
Conjunctival haemorrhage	2/44 (4.5%)
Ocular discomfort	2/44 (4.5%)
Retinal haemorrhage	3/44 (6.8%)
Gastrointestinal disorders
Abdominal pain upper	3/44 (6.8%)
Constipation	2/44 (4.5%)
Diarrhoea	11/44 (25%)
Flatulence	2/44 (4.5%)
Gastritis	2/44 (4.5%)
Gingival bleeding	2/44 (4.5%)
Gingival pain	2/44 (4.5%)
Toothache	3/44 (6.8%)
Vomiting	3/44 (6.8%)
General disorders
Chest discomfort	5/44 (11.4%)
Chest pain	2/44 (4.5%)
Fatigue	3/44 (6.8%)
Oedema peripheral	4/44 (9.1%)
Pyrexia	6/44 (13.6%)
Infections and infestations
Bronchitis	2/44 (4.5%)
Conjunctivitis	2/44 (4.5%)
Herpes zoster	3/44 (6.8%)
Nasopharyngitis	6/44 (13.6%)
Periodontitis	2/44 (4.5%)
Pharyngitis	2/44 (4.5%)
Pneumonia	9/44 (20.5%)
Sinusitis	2/44 (4.5%)
Tonsillitis	2/44 (4.5%)
Upper respiratory tract infection	12/44 (27.3%)
Urinary tract infection	8/44 (18.2%)
Injury, poisoning and procedural complications
Fracture	2/44 (4.5%)
Limb injury	2/44 (4.5%)
Investigations
Alanine aminotransferase increased	5/44 (11.4%)
Aspartate aminotransferase increased	5/44 (11.4%)
Bilirubin conjugated increased	2/44 (4.5%)
Blood alkaline phosphatase increased	2/44 (4.5%)
Blood bilirubin increased	2/44 (4.5%)
Blood creatinine increased	2/44 (4.5%)
Blood immunoglobulin M increased	2/44 (4.5%)
Carbon dioxide increased	2/44 (4.5%)
Electrocardiogram QT prolonged	2/44 (4.5%)
Gamma-glutamyltransferase increased	3/44 (6.8%)
Lymphocyte count decreased	4/44 (9.1%)
Neutrophil count decreased	26/44 (59.1%)
Platelet count decreased	13/44 (29.5%)
Weight decreased	3/44 (6.8%)
Weight increased	10/44 (22.7%)
White blood cell count decreased	14/44 (31.8%)
White blood cells urine positive	3/44 (6.8%)
Metabolism and nutrition disorders
Decreased appetite	7/44 (15.9%)
Glucose tolerance impaired	2/44 (4.5%)
Hyperglycaemia	5/44 (11.4%)
Hyperuricaemia	4/44 (9.1%)
Hypoalbuminaemia	6/44 (13.6%)
Hypocalcaemia	2/44 (4.5%)
Hypokalaemia	6/44 (13.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/44 (20.5%)
Back pain	4/44 (9.1%)
Nervous system disorders
Dizziness	4/44 (9.1%)
Headache	3/44 (6.8%)
Psychiatric disorders
Insomnia	2/44 (4.5%)
Renal and urinary disorders
Haematuria	3/44 (6.8%)
Respiratory, thoracic and mediastinal disorders
Cough	6/44 (13.6%)
Epistaxis	4/44 (9.1%)
Interstitial lung disease	2/44 (4.5%)
Oropharyngeal pain	4/44 (9.1%)
Productive cough	3/44 (6.8%)
Pulmonary mass	2/44 (4.5%)
Skin and subcutaneous tissue disorders
Ecchymosis	4/44 (9.1%)
Haemorrhage subcutaneous	2/44 (4.5%)
Neurodermatitis	2/44 (4.5%)
Petechiae	2/44 (4.5%)
Purpura	8/44 (18.2%)
Rash	8/44 (18.2%)
Skin haemorrhage	2/44 (4.5%)
Vascular disorders
Hypertension	8/44 (18.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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