Trial Outcomes & Findings for Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL) (NCT NCT03206970)
NCT ID: NCT03206970
Last Updated: 2024-10-26
Results Overview
The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR.
COMPLETED
PHASE2
86 participants
Up to 1 year and 11 months
2024-10-26
Participant Flow
This study was conducted at 14 study centers in China; 13 study centers enrolled participants. Once the primary and secondary objectives were met and the analysis was complete, sponsor ended the study on 08 September 2020 and transferred all participants remaining on treatment to long term extension study.
Participant milestones
| Measure |
Zanubrutinib
Zanubrutinib (160 milligrams \[mg\]) administered orally twice daily (BID) until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Overall Study
STARTED
|
86
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
86
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
86
|
Reasons for withdrawal
| Measure |
Zanubrutinib
Zanubrutinib (160 milligrams \[mg\]) administered orally twice daily (BID) until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Overall Study
Death
|
21
|
|
Overall Study
Withdrawal by Subject
|
13
|
|
Overall Study
Lost to Follow-up
|
3
|
|
Overall Study
Primary and secondary objectives were met and remaining participants transferred to LTE by sponsor
|
49
|
Baseline Characteristics
Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Baseline characteristics by cohort
| Measure |
Zanubrutinib
n=86 Participants
Zanubrutinib (160 mg) administered BID until Zanubrutinib (160 milligrams \[mg\]) administered orally twice daily (BID) until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Age, Continuous
|
59.0 years
STANDARD_DEVIATION 8.18 • n=5 Participants
|
|
Age, Customized
< 65 years
|
64 Participants
n=5 Participants
|
|
Age, Customized
≥ 65 years
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
67 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Chinese
|
86 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
86 participants
n=5 Participants
|
|
Mantle Cell Lymphoma (MCL) Disease Stage at Study Entry
MCL Stage I
|
1 Participants
n=5 Participants
|
|
Mantle Cell Lymphoma (MCL) Disease Stage at Study Entry
MCL Stage II
|
7 Participants
n=5 Participants
|
|
Mantle Cell Lymphoma (MCL) Disease Stage at Study Entry
MCL Stage III
|
14 Participants
n=5 Participants
|
|
Mantle Cell Lymphoma (MCL) Disease Stage at Study Entry
MCL Stage IV
|
64 Participants
n=5 Participants
|
|
Disease Status
Relapsed Disease
|
41 Participants
n=5 Participants
|
|
Disease Status
Refractory Disease
|
45 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status
Grade 0
|
60 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status
Grade 1
|
22 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group Performance Status
Grade 2
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 1 year and 11 monthsPopulation: Safety Analysis Set: All participants who received any dose of study drug.
The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR). The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR.
Outcome measures
| Measure |
Zanubrutinib
n=86 Participants
Zanubrutinib (160 mg) administered BID until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Overall Response Rate (ORR) As Assessed By Independent Review Committee
|
72 Participants
|
SECONDARY outcome
Timeframe: Up to 3 years and 6 monthsPopulation: Safety Analysis Set: All participants who received any dose of study drug.
Progression-free survival was defined as the time from the starting date of zanubrutinib to the date of first documentation of disease progression or death, whichever occurred first. Participants who did not have disease progression were censored at their last valid tumor assessment. A six-month progression-free survival rate was defined as no disease progression after treated with zanubrutinib for over six months (under control). The 95% confidence interval (CI) lower bound was 33.1 months while the upper bound could not be estimated.
Outcome measures
| Measure |
Zanubrutinib
n=86 Participants
Zanubrutinib (160 mg) administered BID until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Progression-free Survival
|
33.0 months
Interval 19.4 to
NA = Not estimable due to insufficient number of participants with events
|
SECONDARY outcome
Timeframe: Up to 3 years and 6 monthsPopulation: Safety Analysis Set: All participants who received any dose of study drug.
Time to response was defined as the time from treatment initiation to the first documentation of response.
Outcome measures
| Measure |
Zanubrutinib
n=72 Participants
Zanubrutinib (160 mg) administered BID until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Time To Response
|
2.72 months
Standard Deviation 0.105
|
SECONDARY outcome
Timeframe: Up to 3 years and 6 monthsPopulation: Safety Analysis Set: All participants who received any dose of study drug.
The duration of response was defined as the time from the date that the response criteria are first met to the date that Progressive Disease was objectively documented or death (whichever occurs first). Participants who did not have disease progression were censored at their last valid assessment.
Outcome measures
| Measure |
Zanubrutinib
n=86 Participants
Zanubrutinib (160 mg) administered BID until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Duration Of Response
|
NA months
Interval 24.9 to
NA = Not estimable due to insufficient number of participants with events
|
SECONDARY outcome
Timeframe: Up to 3 years and 6 monthsPopulation: Safety Analysis Set: All participants who received any dose of study drug.
The ORR was assessed in accordance with the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The ORR was defined as the percentage of participants achieving a BOR of CR or PR. The BOR was defined as the best response recorded from the start of zanubrutinib until data cut or start of new antineoplastic treatment. Participants with no post-baseline response assessment (due to any reason) were considered non-responders for BOR. For this outcome measure, only investigator-assessed data are analyzed and reported because of the high rate of concordance between the Independent Review Committee and investigator assessments for the primary outcome measure of ORR.
Outcome measures
| Measure |
Zanubrutinib
n=86 Participants
Zanubrutinib (160 mg) administered BID until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
ORR As Assessed By The Investigator
|
72 Participants
|
SECONDARY outcome
Timeframe: From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)Population: Safety Analysis Set: All participants who received any dose of study drug.
An AE was 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. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date or a worsening in severity from baseline (pretreatment) on or after the date of first dose of study drug up to 30 days following study drug discontinuation (Safety Follow-up visit) or initiation of new anticancer therapy, whichever comes first.
Outcome measures
| Measure |
Zanubrutinib
n=86 Participants
Zanubrutinib (160 mg) administered BID until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Number Of Participants Experiencing Treatment -Emergent Adverse Events (AEs)
|
83 Participants
|
SECONDARY outcome
Timeframe: From the initiation of study drug until 30 days after the last dose (Up to 3 years and 6 months)Population: Safety Analysis Set: All participants who received any dose of study drug.
An AE was 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 the study drug or not. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Zanubrutinib
n=86 Participants
Zanubrutinib (160 mg) administered BID until disease progression, unacceptable toxicity or death, withdrawal of consent, lost to follow up, or study termination by sponsor, which comes first.
|
|---|---|
|
Number Of Participants Experiencing AEs Leading To Treatment Discontinuation
|
8 Participants
|
Adverse Events
Zanubrutinib
Serious adverse events
| Measure |
Zanubrutinib
n=86 participants at risk
Zanubrutinib (160 mg) administered BID for over 3 years.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Blood and lymphatic system disorders
Bone marrow necrosis
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
2.3%
2/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
General disorders
Death
|
2.3%
2/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Bronchitis
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Infection
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Pneumonia
|
11.6%
10/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Pneumonia fungal
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Pneumonia klebsiella
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Upper respiratory tract infection
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Urinary tract infection
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Neutrophil count decreased
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Platelet count decreased
|
2.3%
2/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Nervous system disorders
Cerebral ischaemia
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Nervous system disorders
Transient ischaemic attack
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Renal and urinary disorders
Ureterolithiasis
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
1.2%
1/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
Other adverse events
| Measure |
Zanubrutinib
n=86 participants at risk
Zanubrutinib (160 mg) administered BID for over 3 years.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
16.3%
14/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Blood and lymphatic system disorders
Leukopenia
|
8.1%
7/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.1%
7/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
9.3%
8/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Gastrointestinal disorders
Abdominal pain
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Gastrointestinal disorders
Constipation
|
7.0%
6/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Gastrointestinal disorders
Diarrhoea
|
16.3%
14/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Gastrointestinal disorders
Toothache
|
7.0%
6/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
General disorders
Oedema peripheral
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
General disorders
Peripheral swelling
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
General disorders
Pyrexia
|
8.1%
7/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Asymptomatic bacteriuria
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Folliculitis
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Otitis media
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Pharyngitis
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Upper respiratory tract infection
|
38.4%
33/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Urinary tract infection
|
11.6%
10/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.8%
5/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Alanine aminotransferase increased
|
18.6%
16/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Aspartate aminotransferase increased
|
10.5%
9/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Blood bilirubin increased
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Blood creatinine increased
|
9.3%
8/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Blood immunoglobulin G decreased
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Blood urine present
|
12.8%
11/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Lymphocyte count decreased
|
5.8%
5/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Neutrophil count decreased
|
45.3%
39/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Platelet count decreased
|
32.6%
28/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Weight decreased
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
Weight increased
|
8.1%
7/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Investigations
White blood cell count decreased
|
33.7%
29/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
14.0%
12/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
14.0%
12/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
17.4%
15/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Psychiatric disorders
Insomnia
|
5.8%
5/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Renal and urinary disorders
Haematuria
|
7.0%
6/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.6%
10/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Rash
|
36.0%
31/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Vascular disorders
Hypertension
|
15.1%
13/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Pneumonia
|
8.1%
7/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Infections and infestations
Nasopharyngitis
|
5.8%
5/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
General disorders
Chest discomfort
|
3.5%
3/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
|
Nervous system disorders
Headache
|
4.7%
4/86 • Day 1 through 3 years and 6 months
Safety Analysis Set
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
- Publication restrictions are in place
Restriction type: OTHER