MAGNOLIA: Study of Zanubrutinib (BGB-3111) in Participants With Marginal Zone Lymphoma

• Sponsor: BeiGene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03846427
• Collaborator: (none)
• Enrollment: 68
• Locations: 29
• Arm: 1
• Actual Duration (Months): 38.4
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a single arm study to evaluate the efficacy, safety and tolerability of zanubrutinib (BGB-3111) in participants with relapsed/refractory marginal zone lymphoma (R/R MZL).

Condition or Disease	Intervention/Treatment	Phase
Marginal Zone Lymphoma	Drug: Zanubrutinib	Phase 2

Detailed Description

This is a Phase 2, open-label study of zanubrutinib in approximately 65 participants with R/R MZL. The study will evaluate efficacy, as measured by overall response rate, safety and tolerability.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-label Study of Zanubrutinib (BGB-3111) in Patients With Relapsed or Refractory Marginal Zone Lymphoma
• Actual Study Start Date: Feb 19, 2019
• Actual Primary Completion Date: Jan 18, 2021
• Actual Study Completion Date: May 4, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zanubrutinib	Drug: Zanubrutinib; Zanubrutinib at a dose of 160 mg orally twice a day (BID); Other Names: BGB-3111 Brukinsa

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) by Independent Review Committee [Up to 21.9 months (as of the primary data cutoff date of 18 January 2021)]

   ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by an independent review committee using the Lugano Classification

Secondary Outcome Measures

1. ORR by Investigator Assessment [Up to approximately 3 years and 2 months]

   ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by investigator assessment using the Lugano Classification

2. Progression-free Survival (PFS) [Up to approximately 3 years and 2 months]

   PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator and an independent review committee using Lugano Classification

3. Overall Survival (OS) [Up to approximately 3 years and 2 months]

   OS is defined as the time from first study drug administration to the date of death due to any cause

4. Duration of Response (DOR) [Up to approximately 3 years and 2 months]

   DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator and an independent review committee using Lugano Classification

5. Time to Response (TTR) [Up to approximately 3 years and 2 months]

   TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better), as assessed by the investigator and an independent review committee using Lugano Classification

6. Time to Treatment Failure (TTF) [Up to approximately 3 years and 2 months]

   TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason

7. Time to Next Line of Therapy [Up to approximately 3 years and 2 months]

   Time to next line of therapy is defined as the time from study treatment start to the start of the first subsequent therapy for MZL

8. Quality of Life Assessment: EQ-5D-5L Visual Analogue Score [Up to approximately 3 years and 2 months]

   Mean change from baseline in EuroQol (EQ-5D-5L) visual analogue score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.

9. Quality of Life Assessment: EORTC QLQ-C30 Global Health Status [Up to approximately 3 years and 2 months]

   Mean change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients and includes global health status and quality of life questions related to their overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. A higher score indicates better health outcomes.

10. Number of Participants With Adverse Events [Up to approximately 3 years and 2 months]

    Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, physical exams, and vital signs

11. Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of Zanubrutinib [Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle)]

12. Apparent Oral Clearance (CL/F) of Zanubrutinib [Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle)]

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

1. Age 18 years or older

2. Histologically confirmed diagnosis of MZL including splenic, nodal, and extranodal subtypes

3. Previously received one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least partial response or documented progressive disease (PD) after, the most recent systemic treatment

4. Current need for systemic therapy for MZL

5. Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI)

6. Eastern Cooperative Oncology Group (ECOG) of 0-2

7. Life expectancy ≥ 6 months

8. Adequate bone marrow function

9. Adequate organ function

10. Male and female participants must use highly effective methods of contraception

Key Exclusion Criteria:

1. Known transformation to aggressive lymphoma, eg, large cell lymphoma.

2. Clinically significant cardiovascular disease

3. Prior malignancy within the past 2 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer

4. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention

5. History of stroke or intracranial hemorrhage

6. Severe or debilitating pulmonary disease

7. Active fungal, bacterial and/or viral infection requiring systemic therapy

8. Known central nervous system involvement by lymphoma

9. Known infection with HIV, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection

10. Major surgery within 4 weeks of the first dose of study drug

11. Prior treatment with a Bruton tyrosine kinase (BTK) inhibitor

12. Pregnant or lactating women

13. Requires ongoing treatment with a strong Cytochrome P4503A (CYP3A) inhibitor or inducer

14. Concurrent participation in another therapeutic clinical trial

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Alliance	Lake Success	New York	United States	11042
2	Levine Cancer Institute - Carolinas Medical Center	Charlotte	North Carolina	United States	28204
3	Concord Repatriation General Hospital	Concord	New South Wales	Australia
4	St George Hospital	Kogarah	New South Wales	Australia
5	Princess Alexandra Hospital (AUS)	Woolloongabba	Queensland	Australia
6	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
7	Box Hill Hospital (AUS)	Box Hill	Victoria	Australia
8	Peninsula Private Hospital	Frankston	Victoria	Australia
9	Monash Medical Centre	Clayton		Australia	3168
10	Canberra Hospital	Garran		Australia	2605
11	Henan Cancer Hospital	Zhengzhou	Henan	China
12	Institute of Hematology and Hospital of Blood Disease	Tianjin	Tianjin	China	300020
13	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang	China
14	Peking University Third Hospital	Beijing		China
15	Fakultni nemocnice Kralovske Vinohrady	Praha 10		Czechia	100 34
16	Hopital de la Conception - APHM	Marseille Cedex 05	Bouches-du-Rhône	France	13005
17	Hôpital Saint-Louis	Paris		France	75475
18	Centre Hospitalier Lyon Sud	Pierre-Bénite		France	69495
19	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna		Italy	40138
20	Azienda Socio Sanitaria Territoriale Niguarda (Grande Ospedale Metropolitano Niguarda)	Milano		Italy	20162
21	A.O.U. Policlinico di Modena	Modena		Italy	41124
22	Azienda Ospedaliero - Universitaria Maggiore delle Carità	Novara		Italy	28100
23	Azienda Ospedaliera S. Maria Di Terni	Terni		Italy	05100
24	North Shore Hospital (NZ)	Auckland		New Zealand	0620
25	Auckland City Hospital	Auckland		New Zealand	1023
26	University College London Hospitals	London	Greater London	United Kingdom	WC1N 3BG
27	Royal Marsden Hospital- London	London	Greater Longon	United Kingdom	SW3 6JJ
28	The Christie	Manchester	Greater Manchester	United Kingdom	M20 4BX
29	Beatson West of Scotland Cancer Centre	Glasgow	Strathclyde	United Kingdom	G12 OYN

Sponsors and Collaborators

• BeiGene

Investigators

• Principal Investigator: Study Director, BeiGene

Study Documents (Full-Text)

• Study Protocol - Jun 3, 2020
• Statistical Analysis Plan - Jun 10, 2020

More Information

Publications

• Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. doi: 10.1158/1078-0432.CCR-21-1704. Epub 2021 Sep 15.
• Stephen Opat, et al. Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory Marginal Zone Lymphoma: Initial Results of the MAGNOLIA (BGB-3111-214) Trial. Presented at the 62nd American Society of Hematology (ASH) Annual Meeting, December 5-8, 2020. Abstract 339.
• Stephen Opat, Robert Marcus, MA, FRCP, FRCPath, Craig A. Portell, MD, William Reed, MD, Chris Tankersley, Jane Huang, MD, Judith Trotman, MBChB, FRACP, FRCPA. Phase 2 Study of Zanubrutinib (BGB-3111) in Patients with Relapsed/Refractory Marginal Zone Lymphoma. Blood. 2019; 134(1):5256. https://doi.org/10.1182/blood-2019-122629

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT03846427
• Other Study ID Numbers: BGB-3111-214; 2018-001284-24; CTR20180823
• First Posted: Feb 19, 2019
• Last Update Posted: Jun 30, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by BeiGene: BGB-3111; Zanubrutinib
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell, Marginal Zone; Zanubrutinib

Study Results

Participant Flow

Recruitment Details	The first participant was dosed on 19 February 2019, and the last participant enrolled received their first dose on 06 January 2020. The median study follow-up time as of the primary data cutoff date of 18 January 2021 was 15.7 months (range: 1.6 to 21.9 months).

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent
Period Title: Overall Study
STARTED	68
COMPLETED	0
NOT COMPLETED	68

Baseline Characteristics

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent
Overall Participants	68
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.9 (11.41)
Sex: Female, Male (Count of Participants)
Female	32 47.1%
Male	36 52.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	59 86.8%
Unknown or Not Reported	9 13.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	13 19.1%
White	41 60.3%
Multiple	2 2.9%
Other	1 1.5%
Unknown	1 1.5%
Not Reported	10 14.7%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR) by Independent Review Committee
Description	ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by an independent review committee using the Lugano Classification
Time Frame	Up to 21.9 months (as of the primary data cutoff date of 18 January 2021)

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set included all participants who were enrolled, received at least 1 dose of study drug, and had a confirmed diagnosis of MZL.

Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent
Measure Participants	66
Number (95% Confidence Interval) [Percentage of participants]	68.2 100.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zanubrutinib
	Comments
	Type of Statistical Test	Superiority
	Comments	P value was based on the exact binomial test against the null hypothesis of ORR = 30% with alternative of ORR > 30% at a significance level of 0.025 (1-sided)
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact binomial test
	Comments

2. Secondary Outcome

Title	ORR by Investigator Assessment
Description	ORR is defined as the percentage of participants with complete or partial response as the best overall response, as determined by investigator assessment using the Lugano Classification
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. 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 the investigator and an independent review committee using Lugano Classification
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from first study drug administration to the date of death due to any cause
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. 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 progressive disease is objectively documented or death, whichever comes first, as assessed by the investigator and an independent review committee using Lugano Classification
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better), as assessed by the investigator and an independent review committee using Lugano Classification
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Time to Treatment Failure (TTF)
Description	TTF is defined as the time from study treatment start to the date of discontinuation of study drug due to any reason
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Time to Next Line of Therapy
Description	Time to next line of therapy is defined as the time from study treatment start to the start of the first subsequent therapy for MZL
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Quality of Life Assessment: EQ-5D-5L Visual Analogue Score
Description	Mean change from baseline in EuroQol (EQ-5D-5L) visual analogue score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Quality of Life Assessment: EORTC QLQ-C30 Global Health Status
Description	Mean change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients and includes global health status and quality of life questions related to their overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. A higher score indicates better health outcomes.
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory tests, physical exams, and vital signs
Time Frame	Up to approximately 3 years and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Area Under the Curve From Time 0 to 12 Hours (AUC0-12) of Zanubrutinib
Time Frame	Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Apparent Oral Clearance (CL/F) of Zanubrutinib
Time Frame	Predose (within 30 min prior to dose) and 0.5, 1, 2, 3, 4, and 6 hours postdose on Cycle 1 Day 1 (28 days per cycle)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 21.9 months (as of the primary data cutoff date of 18 January 2021)
Arm/Group Title	Zanubrutinib
Arm/Group Description	Zanubrutinib 160 mg (two 80-mg capsules) orally twice daily with or without food until progressive disease, intolerable toxicity, or withdrawal of consent
All Cause Mortality
	Zanubrutinib
	Affected / at Risk (%)	# Events
Total	7/68 (10.3%)
Serious Adverse Events
	Zanubrutinib
	Affected / at Risk (%)	# Events
Total	26/68 (38.2%)
Blood and lymphatic system disorders
Anaemia	1/68 (1.5%)
Pancytopenia	1/68 (1.5%)
Cardiac disorders
Angina pectoris	1/68 (1.5%)
Atrial fibrillation	1/68 (1.5%)
Atrial flutter	1/68 (1.5%)
Coronary artery stenosis	1/68 (1.5%)
Myocardial infarction	1/68 (1.5%)
Gastrointestinal disorders
Abdominal pain upper	1/68 (1.5%)
Colitis	1/68 (1.5%)
Gastrooesophageal reflux disease	1/68 (1.5%)
Small intestinal obstruction	1/68 (1.5%)
General disorders
Asthenia	1/68 (1.5%)
Chest pain	1/68 (1.5%)
Pyrexia	3/68 (4.4%)
Hepatobiliary disorders
Bile duct stone	1/68 (1.5%)
Cholecystitis	1/68 (1.5%)
Infections and infestations
Bronchitis	1/68 (1.5%)
COVID-19 pneumonia	3/68 (4.4%)
Influenza	1/68 (1.5%)
Pneumonia	1/68 (1.5%)
Respiratory syncytial virus infection	1/68 (1.5%)
Sinusitis	1/68 (1.5%)
Tonsillitis	1/68 (1.5%)
Tuberculosis	1/68 (1.5%)
Urinary tract infection	1/68 (1.5%)
Injury, poisoning and procedural complications
Acetabulum fracture	1/68 (1.5%)
Fall	2/68 (2.9%)
Humerus fracture	1/68 (1.5%)
Pelvic fracture	1/68 (1.5%)
Investigations
Platelet count decreased	1/68 (1.5%)
Metabolism and nutrition disorders
Hyperkalaemia	1/68 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer recurrent	1/68 (1.5%)
Papillary thyroid cancer	1/68 (1.5%)
Nervous system disorders
Ischaemic stroke	1/68 (1.5%)
Sciatica	1/68 (1.5%)
Syncope	1/68 (1.5%)
Vertebrobasilar insufficiency	1/68 (1.5%)
Renal and urinary disorders
Acute kidney injury	1/68 (1.5%)
Respiratory, thoracic and mediastinal disorders
Organising pneumonia	1/68 (1.5%)
Respiratory failure	1/68 (1.5%)
Other (Not Including Serious) Adverse Events
	Zanubrutinib
	Affected / at Risk (%)	# Events
Total	56/68 (82.4%)
Blood and lymphatic system disorders
Anaemia	3/68 (4.4%)
Neutropenia	5/68 (7.4%)
Thrombocytopenia	6/68 (8.8%)
Gastrointestinal disorders
Abdominal pain	8/68 (11.8%)
Constipation	10/68 (14.7%)
Diarrhoea	15/68 (22.1%)
Gastrooesophageal reflux disease	3/68 (4.4%)
Nausea	7/68 (10.3%)
Vomiting	3/68 (4.4%)
General disorders
Fatigue	6/68 (8.8%)
Oedema peripheral	3/68 (4.4%)
Pyrexia	7/68 (10.3%)
Infections and infestations
Oral herpes	3/68 (4.4%)
Tonsillitis	3/68 (4.4%)
Upper respiratory tract infection	8/68 (11.8%)
Urinary tract infection	3/68 (4.4%)
Injury, poisoning and procedural complications
Contusion	14/68 (20.6%)
Investigations
Alanine aminotransferase increased	3/68 (4.4%)
Neutrophil count decreased	4/68 (5.9%)
Platelet count decreased	4/68 (5.9%)
Metabolism and nutrition disorders
Hypokalaemia	3/68 (4.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/68 (8.8%)
Back pain	7/68 (10.3%)
Musculoskeletal pain	3/68 (4.4%)
Myalgia	3/68 (4.4%)
Pain in extremity	3/68 (4.4%)
Nervous system disorders
Dizziness	4/68 (5.9%)
Lethargy	4/68 (5.9%)
Paraesthesia	3/68 (4.4%)
Respiratory, thoracic and mediastinal disorders
Cough	4/68 (5.9%)
Epistaxis	3/68 (4.4%)
Skin and subcutaneous tissue disorders
Petechiae	3/68 (4.4%)

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.