A Study of Tislelizumab as Monotherapy in Relapsed or Refractory Classical Hodgkin Lymphoma

• Sponsor: BeiGene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03209973
• Collaborator: (none)
• Enrollment: 70
• Locations: 11
• Arm: 1
• Actual Duration (Months): 42.4
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study was to evaluate the efficacy of tislelizumab assessed by Independent Review Committee (IRC) in participants with relapsed or refractory classical Hodgkin lymphoma (cHL), as measured by Overall Response Rate (ORR) per the Lugano Classification

Condition or Disease	Intervention/Treatment	Phase
Classical Hodgkin Lymphoma	Drug: Tislelizumab	Phase 2

Detailed Description

This was an open-label, single-arm, multi-center Phase 2 study. Response was to be assessed by PET(positron emission tomography) and computed tomography (CT) scan per the Lugano Classification. CT scan with contrast and Positron emission tomography (PET)/CT was used as required by protocol, until progressive disease (PD), new anti-cancer therapy, withdrawal of consent, death, lost to follow-up, or end of study (EOS), whichever occurred first. Total body magnetic resonance imaging (MRI) was allowed if CT with contrast is contraindicated. During treatment with immune checkpoint inhibitor such as with tislelizumab, pseudo-progression may occur due to immune cell infiltration and other mechanisms as manifested by apparent increase of existing tumor masses or appearance of new tumor lesions. Participants were allowed to continue study treatment if there is suspicion of pseudo-progression, provided they are asymptomatic and have radiographic progression only, until a second consecutive CT scan demonstrates PD at which time study treatment was discontinued permanently. Participants were evaluated for Adverse Events (AEs) (all Grades per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 [NCI CTCAE v. 4.03]), serious AEs (SAEs), and any AEs requiring study drug interruption or discontinuation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Arm, Multicenter, Phase 2 Study of BGB-A317 as Monotherapy in Relapsed or Refractory Classical Hodgkin Lymphoma
• Actual Study Start Date: Apr 21, 2017
• Actual Primary Completion Date: Nov 2, 2020
• Actual Study Completion Date: Nov 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tislelizumab Tislelizumab 200 mg administered intravenously (IV) every-3-weeks (Q3W)	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [From the date of first dose Up to approximately 3 year and 7 months]

   ORR is defined as the proportion of participants who achieve a best response of Complete Response (CR) or Partial Response (PR), as assessed by Independent Review committee (IRC) per the Lugano Classification

Secondary Outcome Measures

1. Progression-free Survival (PFS) [From the date of first dose until end of study (Up to approximately 3 years and 7 months)]

   PFS is defined as the time from the first dose of tislelizumab to the date of Progressive Disease (PD) or death, whichever occurs first, assessed by IRC per the Lugano Classification

2. Duration of Response (DOR) [From the date of first dose until end of study (Up to approximately 3 years and 7 months)]

   DOR is defined as the time from the date that response criteria are first met to the date that PD is objectively documented or death, whichever occurs first, assessed by IRC per the Lugano Classification

3. Rate of Complete Response (CRR) [From the date of first dose until end of study (Up to approximately 3 years and 7 months)]

   CRR is defined as the percentage of participants who achieve a best response of CR, assessed by IRC per the Lugano Classification

4. Time to Response (TTR) [From the date of first dose until end of study (Up to approximately 3 years and 7 months)]

   TTR is defined as the time from the date of the first dose of tislelizumab to the time the response criteria are first met, assessed by IRC per the Lugano Classification

5. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From the date of first dose until end of study (Up to approximately 3 years and 7 months)]

   An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. An SAE is any untoward medical occurrence that, at any dose: Results in death. Is life-threatening. Requires hospitalization or prolongation of existing hospitalization Results in disability/incapacity Is a congenital anomaly/birth defect Is considered a significant medical AE by the investigator based on medical judgement

6. Number of Participants With Significant Changes in Clinical Laboratory Results [From the date of first dose until end of study (Up to approximately 3 years and 7 months)]

   Clinical laboratory (e.g. hematology, serum chemistry, urinalysis) values were evaluated for each laboratory parameter and participants with clinically significant changes are summarized.

7. Number of Participants With Significant Changes in Electrocardiograms [From the date of first dose until end of study (Up to approximately 3 years and 7 months)]

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

1. Histologically confirmed relapsed or refractory cHL (biopsy from diagnosis or at any relapse is acceptable).

2. Participants must have relapsed (disease progression after most recent therapy) or refractory (failure to achieve complete Response (CR) /complete metabolic response [CMR] or partial response (PR) to most recent therapy) cHL and and failed to achieve a response or progressed after auto-SCT or meet the criteria of ineligible for auto-SCT.

3. Participants must have measurable disease defined as ≥ 1 nodal lesion that is > 1.5 cm in the longest diameter, or ≥ 1 extra-nodal lesion (e.g. hepatic nodules) that is > 1 cm in the longest diameter.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. Life expectancy ≥ 12 weeks.

6. participants must have adequate organ functions as indicated by the following laboratory values:

7. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, independent of growth factor support within 7 days of first dose.

8. Platelet ≥ 75 x 109/L, independent of growth factor support or transfusion within 7 days of first dose.

9. Hemoglobin (Hgb) ≥ 8 g/dL or ≥ 5 mmol/L.

10. Serum creatinine ≤ 1.5 x upper limit of normal (ULN).

11. Aspartate aminotransferase (AST)/glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x upper limit of normal (ULN), or ≤ 5X ULN if liver metastases are present.

12. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin level < 4 x ULN for participants with Gilbert's syndrome).

13. International normalized ratio (INR) ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy and coagulation parameters (prothrombin time [PT/INR] and aPTT) are within intended therapeutic range of intended use of the anticoagulant at time of Screening. Participants with factor inhibitors prolonging PT or INR may be included after discussion with the medical monitor.

14. Participants must have no evidence of dyspnea at rest and a pulse oximetry of > 92% while breathing room air.

15. Participants must have forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT); carbon monoxide diffusion capacity (DLCO), FEV1 and FVC all > 50 % predicted value; all PFTs must be obtained within 4 weeks prior to the first dose of tislelizumab.

16. Prior chemotherapy, radiotherapy, immunotherapy or investigational therapy (including Chinese herbal medicine and Chinese patent medicine) used to control cancer including locoregional treatment must have been completed ≥ 4 weeks before the first dose of tislelizumab, and all treatment-related adverse events are stable and have either returned to baseline or Grade 0/1 (except for alopecia and hemoglobin. For hemoglobin, please follow inclusion criteria #8c [hemoglobin]).

Key Exclusion Criteria:

1. Nodular lymphocyte-predominant Hodgkin lymphoma or gray zone lymphoma.

2. Prior allogeneic hematopoietic stem cell transplant.

3. History of severe hypersensitivity reaction to monoclonal antibodies.

4. New York Heart Association (NYHA) class III or IV heart failure, unstable angina, severe uncontrolled ventricular arrhythmia, electrocardiographic evidence of acute ischemia, or myocardial infarction within 6 months of first day of Screening.

5. Prior malignancy within the past 3 years except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast.

6. Prior therapy targeting PD-1 or PD-L1.

7. Participants with active autoimmune disease or history of autoimmune disease with high risk of recurrence including but not limited to history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barrè syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome.

Note: Participants is permitted to enroll if he/she has vitiligo, eczema, type I diabetes mellitus, endocrine deficiencies including thyroiditis managed with replacement hormone and/or physiologic corticosteroid. Participants with rheumatoid arthritis and/or other arthropathies, Sjögren's syndrome or psoriasis controlled with topical medication, and participants with positive serology such as positive antinuclear antibody (ANA) or anti-thyroid antibody should be evaluated for presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.

1. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily Prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of tislelizumab.

Note: Adrenal replacement doses of ≤ 10 mg daily Prednisone are permitted in the absence of active autoimmune disease. Topical, ocular, intra-articular, intra-nasal and inhalational corticosteroid (with minimal systemic absorption), a brief course of corticosteroid for prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by contact allergen) are allowed.

1. Has history of interstitial lung disease or non-infectious pneumonitis or has evidence of interstitial lung disease or non infectious pneumonitis currently.

2. QT Interval Corrected by the Fridericia Correction Formula (QTcF)interval > 480 msec, unless secondary to bundle branch block.

3. Serious acute or chronic infection requiring systemic therapy.

4. Known central nervous system (CNS) lymphoma.

5. Underlying medical conditions that, in the Investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.

6. Autologous hematopoietic stem cell transplant within 100 days of first dose of tislelizumab.

7. Use of any live vaccine against infectious diseases (e.g. influenza, varicella, etc.) within 4 weeks (28 days) of the first dose of tislelizumab, and any intended use within 60 days after the last dose of tislelizumab.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Cancer Hospital	Beijing	Beijing	China	100142
2	Chinese PLA General Hospital	Beijing	Beijing	China	100853
3	Henan Cancer Hospital	Zhengzhou	Henan	China
4	Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei	China
5	Jiangsu Province Hospital	Nanjing	Jiangsu	China
6	The First Affilliated Hospital of Jilin University	Changchun	Jilin	China
7	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China
8	West China Hospital of Sichuan University	Chengdu	Sichuan	China
9	Institute of Hematology and Blood disease hospital,Chinese Academy of Medical Science	Tianjin	Tianjin	China	300020
10	Tianjin Medical Universtity Cancer Institute and Hospital	Tianjin	Tianjin	China	300060
11	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China

Sponsors and Collaborators

• BeiGene

Investigators

• Principal Investigator: Study Director, BeiGene

Study Documents (Full-Text)

• Study Protocol - Jul 15, 2019
• Statistical Analysis Plan - Jul 17, 2018

More Information

Publications

None provided.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT03209973
• Other Study ID Numbers: BGB-A317-203; CTR20170119
• First Posted: Jul 6, 2017
• Last Update Posted: Nov 18, 2021
• Last Verified: Oct 1, 2021

• 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: Lymphoma; Hodgkin Disease

Study Results

Participant Flow

Recruitment Details	70 participants were enrolled at 11 sites in China. The first participant dose date was on 21 April 2017. The study was completed on 02 November 2020.

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered intravenously (IV) every-3-weeks (Q3W) until progressive disease (PD), unacceptable toxicity, death, or study withdrawal by the participant.
Period Title: Overall Study
STARTED	70
Completed Primary Outcome Period	66
COMPLETED	0
NOT COMPLETED	70

Baseline Characteristics

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered IV Q3W until PD, unacceptable toxicity, death, or study withdrawal by the participant.
Overall Participants	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.2 (12.73)
Age, Customized (Count of Participants)
<65	66 94.3%
≥ 65 and < 75 years	4 5.7%
≥ 75	0 0%
Sex: Female, Male (Count of Participants)
Female	30 42.9%
Male	40 57.1%
Race/Ethnicity, Customized (Count of Participants)
Chinese	70 100%
Region of Enrollment (Count of Participants)
China	70 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	ORR is defined as the proportion of participants who achieve a best response of Complete Response (CR) or Partial Response (PR), as assessed by Independent Review committee (IRC) per the Lugano Classification
Time Frame	From the date of first dose Up to approximately 3 year and 7 months

Outcome Measure Data

Analysis Population Description

Modified Safety Analysis Set: All participants in the safety analysis set who had confirmed classical Hodgkin lymphoma.

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered intravenously (IV) every-3-weeks (Q3W)
Measure Participants	70
Number (95% Confidence Interval) [Percentage of Participants]	87.1 124.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tislelizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	1-sided p-value was based on exact test of BGB-A317 versus historical rate of 0.35
	Method	Exact Binomial Test
	Comments	Comparison with historical control values

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS is defined as the time from the first dose of tislelizumab to the date of Progressive Disease (PD) or death, whichever occurs first, assessed by IRC per the Lugano Classification
Time Frame	From the date of first dose until end of study (Up to approximately 3 years and 7 months)

Outcome Measure Data

Analysis Population Description

Modified Safety Analysis set

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered IV Q3W until PD, unacceptable toxicity, death, or study withdrawal by the participant.
Measure Participants	70
Median (95% Confidence Interval) [Months]	31.5

3. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR is defined as the time from the date that response criteria are first met to the date that PD is objectively documented or death, whichever occurs first, assessed by IRC per the Lugano Classification
Time Frame	From the date of first dose until end of study (Up to approximately 3 years and 7 months)

Outcome Measure Data

Analysis Population Description

Modified Safety Analysis set; Participants with available data were included in the analysis.

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered IV Q3W until PD, unacceptable toxicity, death, or study withdrawal by the participant.
Measure Participants	61
Median (95% Confidence Interval) [Months]	31.3

4. Secondary Outcome

Title	Rate of Complete Response (CRR)
Description	CRR is defined as the percentage of participants who achieve a best response of CR, assessed by IRC per the Lugano Classification
Time Frame	From the date of first dose until end of study (Up to approximately 3 years and 7 months)

Outcome Measure Data

Analysis Population Description

Modified safety analysis set

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered IV Q3W until PD unacceptable toxicity, death, or study withdrawal by the participant.
Measure Participants	70
Median (95% Confidence Interval) [Percentage of participants]	67.1 95.9%

5. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR is defined as the time from the date of the first dose of tislelizumab to the time the response criteria are first met, assessed by IRC per the Lugano Classification
Time Frame	From the date of first dose until end of study (Up to approximately 3 years and 7 months)

Outcome Measure Data

Analysis Population Description

Modified safety analysis set; participants with available data were included in the analysis.

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered IV Q3W until PD, unacceptable toxicity, death, or study withdrawal by the participant.
Measure Participants	61
Median (Full Range) [Weeks]	12.0

6. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not. An SAE is any untoward medical occurrence that, at any dose: Results in death. Is life-threatening. Requires hospitalization or prolongation of existing hospitalization Results in disability/incapacity Is a congenital anomaly/birth defect Is considered a significant medical AE by the investigator based on medical judgement
Time Frame	From the date of first dose until end of study (Up to approximately 3 years and 7 months)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received any dose of tislelizumab.

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered IV Q3W until PD, unacceptable toxicity, death, or study withdrawal by the participant.
Measure Participants	70
Participants with At least one TEAE	68 97.1%
SAE	18 25.7%

7. Secondary Outcome

Title	Number of Participants With Significant Changes in Clinical Laboratory Results
Description	Clinical laboratory (e.g. hematology, serum chemistry, urinalysis) values were evaluated for each laboratory parameter and participants with clinically significant changes are summarized.
Time Frame	From the date of first dose until end of study (Up to approximately 3 years and 7 months)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received any dose of tislelizumab.

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered IV Q3W until PD unacceptable toxicity, death, or study withdrawal by the participant.
Measure Participants	70
Number [Participants]	0 0%

8. Secondary Outcome

Title	Number of Participants With Significant Changes in Electrocardiograms
Time Frame	From the date of first dose until end of study (Up to approximately 3 years and 7 months)

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received any dose of tislelizumab.

Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered IV Q3W until PD unacceptable toxicity, death, or study withdrawal by the participant.
Measure Participants	70
Postbaseline corrected QT interval > 450 msec	0 0%
≥ 1 postbaseline electrocardiogram	21 30%
Increase corrected QT interval of ≤ 30 msec	18 25.7%
Increase > 30 msec but ≤ 60 msec corrected QT interval	4 5.7%

Adverse Events

Time Frame	From the date of first dose until end of study (Up to approximately 3 years and 7 months)
Arm/Group Title	Tislelizumab
Arm/Group Description	Tislelizumab 200 mg administered intravenously (IV) every-3-weeks (Q3W)
All Cause Mortality
	Tislelizumab
	Affected / at Risk (%)	# Events
Total	8/70 (11.4%)
Serious Adverse Events
	Tislelizumab
	Affected / at Risk (%)	# Events
Total	18/70 (25.7%)
Blood and lymphatic system disorders
Neutropenia	1/70 (1.4%)	1
Thrombocytopenia	1/70 (1.4%)	7
Gastrointestinal disorders
Ascites	1/70 (1.4%)	1
General disorders
Death	1/70 (1.4%)	1
Pyrexia	2/70 (2.9%)	2
Infections and infestations
Hepatitis B	1/70 (1.4%)	1
Pneumocystis jirovecii pneumonia	1/70 (1.4%)	1
Pneumonia	2/70 (2.9%)	4
Upper respiratory tract infection	1/70 (1.4%)	1
Urinary tract infection	1/70 (1.4%)	1
Varicella	1/70 (1.4%)	1
Injury, poisoning and procedural complications
Traumatic lung injury	1/70 (1.4%)	1
Investigations
Blood glucose increased	1/70 (1.4%)	1
Metabolism and nutrition disorders
Decreased appetite	1/70 (1.4%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/70 (1.4%)	1
Nervous system disorders
Seizure	1/70 (1.4%)	1
Renal and urinary disorders
Focal segmental glomerulosclerosis	1/70 (1.4%)	1
Hydronephrosis	1/70 (1.4%)	1
Renal injury	1/70 (1.4%)	1
Renal tubular injury	1/70 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	1/70 (1.4%)	2
Organising pneumonia	1/70 (1.4%)	1
Pneumonitis	2/70 (2.9%)	2
Skin and subcutaneous tissue disorders
Erythema nodosum	1/70 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Tislelizumab
	Affected / at Risk (%)	# Events
Total	68/70 (97.1%)
Blood and lymphatic system disorders
Anaemia	9/70 (12.9%)	18
Leukopenia	6/70 (8.6%)	10
Lymphopenia	3/70 (4.3%)	33
Neutropenia	4/70 (5.7%)	6
Thrombocytopenia	4/70 (5.7%)	9
Endocrine disorders
Hyperthyroidism	3/70 (4.3%)	4
Hypothyroidism	26/70 (37.1%)	64
Gastrointestinal disorders
Diarrhoea	10/70 (14.3%)	13
Nausea	6/70 (8.6%)	7
Toothache	3/70 (4.3%)	3
Vomiting	7/70 (10%)	7
General disorders
Asthenia	5/70 (7.1%)	9
Chills	4/70 (5.7%)	4
Pyrexia	40/70 (57.1%)	55
Hepatobiliary disorders
Hepatic function abnormal	4/70 (5.7%)	4
Liver injury	3/70 (4.3%)	7
Infections and infestations
Influenza	4/70 (5.7%)	7
Nasopharyngitis	5/70 (7.1%)	10
Pharyngitis	3/70 (4.3%)	3
Pneumonia	6/70 (8.6%)	7
Upper respiratory tract infection	27/70 (38.6%)	72
Urinary tract infection	3/70 (4.3%)	4
Investigations
Alanine aminotransferase increased	14/70 (20%)	34
Amylase increased	3/70 (4.3%)	17
Aspartate aminotransferase increased	11/70 (15.7%)	16
Bilirubin conjugated increased	6/70 (8.6%)	12
Blood bilirubin increased	7/70 (10%)	19
Blood bilirubin unconjugated increased	5/70 (7.1%)	14
Blood creatine phosphokinase increased	8/70 (11.4%)	15
Blood lactate dehydrogenase increased	4/70 (5.7%)	4
Blood thyroid stimulating hormone increased	8/70 (11.4%)	11
Blood uric acid increased	5/70 (7.1%)	7
Gamma-glutamyltransferase increased	4/70 (5.7%)	5
Lymphocyte count decreased	3/70 (4.3%)	14
Neutrophil count decreased	10/70 (14.3%)	48
Neutrophil count increased	3/70 (4.3%)	5
Platelet count decreased	7/70 (10%)	19
Weight decreased	12/70 (17.1%)	25
Weight increased	24/70 (34.3%)	79
White blood cell count decreased	15/70 (21.4%)	52
White blood cell count increased	4/70 (5.7%)	4
Metabolism and nutrition disorders
Hyperlipidaemia	6/70 (8.6%)	8
Hyperuricaemia	10/70 (14.3%)	21
Hypokalaemia	4/70 (5.7%)	7
Hypoproteinaemia	3/70 (4.3%)	3
Musculoskeletal and connective tissue disorders
Back pain	5/70 (7.1%)	8
Pain in extremity	6/70 (8.6%)	7
Nervous system disorders
Headache	7/70 (10%)	7
Hypoaesthesia	3/70 (4.3%)	4
Paraesthesia	3/70 (4.3%)	3
Respiratory, thoracic and mediastinal disorders
Cough	15/70 (21.4%)	20
Oropharyngeal pain	3/70 (4.3%)	4
Skin and subcutaneous tissue disorders
Pruritus	13/70 (18.6%)	18
Rash	11/70 (15.7%)	15
Vascular disorders
Hypertension	3/70 (4.3%)	5

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.