B-cell Lymphoid Malignancies
Conditions
Keywords
BGB-3111, Zanubrutinib, Obinutuzumab, Lymphoma, Leukemia, Therapeutic uses, B-cell
Brief summary
This study evaluated the safety and preliminary efficacy of BGB-3111 (zanubrutinib) in combination with obinutuzumab in participants with B-cell lymphoid malignancies.
Interventions
DRUGZanubrutinib
DRUGObinutuzumab
Sponsors
BeiGene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged ≥18 years, able and willing to provide written informed consent and to comply with the study protocol. * Laboratory parameters as specified below: * Hematologic: Platelet count \>40x10\^9/liter (L) (may be post-transfusion); absolute neutrophil count \>1.0x10\^9/L (growth factor use is allowed to bring pre-treatment neutrophils to \>1.0x10\^9 cells/L if marrow infiltration is involved). * Hepatic: Total bilirubin \<3 x upper limit normal (ULN); and aspartate aminotransferase and alanine transaminase ≤3 x ULN. * Renal: Creatinine clearance ≥50 milliliters/minute (as estimated by the Cockcroft Gault equation or as measured by nuclear medicine scan or 24-hour urine collection); participants requiring hemodialysis will be excluded. * Anticipated survival of at least 6 months. * Eastern Cooperative Oncology Group performance status of 0 to 2. * Female participants of childbearing potential and non-sterile males must have agreed to practice at least one of the following methods of birth control with partner(s) throughout the study and for ≥3 months after discontinuing zanubrutinib or ≥18 months following obinutuzumab treatment, whichever was longer: total abstinence from sexual intercourse, double barrier contraception, intra uterine device or hormonal contraceptive initiated at least 3 months prior to first administration of study drug. * Male participants must have not donated sperm from first study drug administration, until 3 months after zanubrutinib discontinuation or 18 months following obinutuzumab treatment, whichever is longer.
Exclusion criteria
* Known central nervous system lymphoma or leukemia. * Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome. * Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura. * History of significant cardiovascular disease. * Severe or debilitating pulmonary disease. * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy. * Prior Bruton tyrosine kinase inhibitor treatment. * Used medications which were strong cytochrome P450 (CYP) 3A inhibitors and strong CYP3A inducers. * Vaccination with a live vaccine within 28 days of the initiation of treatment. * Allogeneic stem cell transplantation within 6 months, or had active graft versus host disease requiring ongoing immunosuppression. * Receipt of the following treatment prior to first administration of zanubrutinib, corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or radiotherapy within 3 weeks, monoclonal antibody within 4 weeks. * Participated in any investigational drug study within 28 days of study entry, or not recovered from non-hematologic toxicity of any prior chemotherapy up to ≤ Grade 1 (except for alopecia). * History of other active malignancies within 2 years of study entry. * Major surgery in the past 4 weeks. * Active symptomatic fungal, bacterial and/or viral infection including evidence of infection with human immunodeficiency virus, human T cell lymphotropic virus seropositive status. * Inability to comply with the study procedures. * Pregnant or nursing women. * Any illness or condition that in the opinion of the investigator may have affected the safety of treatment or evaluation of any study's endpoints.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 : Number Of Participants Experiencing Adverse Events | Day 1 (first dose) through 4 years and 8 months | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. A serious AE (SAE) was any untoward medical occurrence that, at any dose. * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect. |
| Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Day -28 to -1 (predose) through 4 years and 8 months | Laboratory results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity. |
| Part 1: Number Of Deaths | Day 1 (first dose) through 4 years and 8 months | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose: * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect. |
| Part 1: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) | Day 1 (first dose) through 4 years and 8 months | Dose-limiting toxicities were defined as a toxicity or AE occurring during the DLT assessment period (first 29 days of treatment), which is not clearly attributable to a cause other than zanubrutinib and/or obinutuzumab (such as disease progression, underlying illness, concurrent illness or concomitant medication) and meets one of the following criteria: * Grade 3 or 4 drug-related non-hematologic toxicity (excluding Grade 3 nausea, vomiting, hypertension, and asymptomatic laboratory abnormalities), * Grade 4 drug-related hematologic toxicity persisting for \>14 days, * any grade toxicity, which in the judgment of the investigator or Sponsor, required removal of the participant from the study. |
| Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Partial Response | Day 1 (first dose) through 4 years and 8 months | Partial response was defined as follows: * ≥ 50% reduction of serum IgM from baseline, * reduction in lymphadenopathy/splenomegaly (if present at baseline). For response assessments that occurred during cycles where a CT scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and Part 2: Hematologic Improvement In Participants With CLL | Day 1 (first dose) through 4 years and 8 months | The number and percentage of participants with CLL with anemia (hemoglobin ≤110 grams/liter \[g/L\]), neutropenia (absolute neutrophil count ≤1.5 x 10\^9/L), or thrombocytopenia (platelet count ≤100 x 10\^9/L) at baseline were estimated. |
| Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUClast) Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To Infinity Time (AUC) Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1: Maximum Plasma Concentration (Cmax) Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1: Time To Maximum Plasma Concentration (Tmax) Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1: Terminal Elimination Half-life (t1/2) Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1: Apparent Clearance (CL/F) Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Complete Response | Day 1 (first dose) through 4 years and 8 months | Complete response was defined as follows: * normal serum IgM values, * disappearance of monoclonal protein by immunofixation, * no histological evidence of bone marrow involvement, * complete resolution of lymphadenopathy/splenomegaly (if present at baseline) For response assessments that occurred during cycles where a computed tomography (CT) scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline. |
| Part 1 and Part 2: Steady State AUClast Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1 and Part 2: Steady State Cmax of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1 and Part 2: Steady State Tmax Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 2: Number Of Participants Experiencing Adverse Events | Day 1 (first dose) through 4 years and 8 months | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose,: * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect. |
| Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Day -28 to -1 (predose) through 4 years and 8 months | Results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity. |
| Part 2: Number Of Deaths | Day 1 (first dose) through 4 years and 8 months | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose,: * resulted in death, * is life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect. |
| Part 1: Apparent Volume Of Distribution (Vz/F) Of Zanubrutinib | Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7 | — |
| Part 1 and Part 2: Progression-free Survival (PFS) | Day 1 (first dose) through 4 years and 8 months | Progression-free survival was defined as time (in months) from the start of treatment with zanubrutinib or obinutuzumab to the first documented disease progression or death due to any cause, whichever occurred first. Results are reported as the median months for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL). |
| Part 1 and Part 2: Duration Of Response (DOR) | Day 1 (first dose) through 4 years and 8 months | Duration of response for responders was defined as the time (in months) from the date of the earliest qualifying response to the date of progressive disease or death due to any cause (whichever occurred earlier). Duration of response was analyzed using the same methods as the analysis for PFS. Responses after initiating new anticancer therapy, roll over to the long-term extension (LTE) study, or the first occurrence of disease progression were not considered in the analysis. |
| Part 1 and Part 2: Time To Response (TTR) | Day 1 (first dose) through 4 years and 8 months | The TTR for responders was defined as time (in months) from the start of the study treatment to the date of the earliest qualifying response. The TTR was summarized using descriptive statistics. Responses after initiating new anticancer therapy, roll over to the LTE study, or the first occurrence of disease progression were not considered in the analysis of TTR. |
| Part 1 and Part 2: Overall Survival (OS) | Day 1 (first dose) through 4 years and 8 months | Overall survival was defined as the time (in months) from the date of the start of the study treatment to death due to any cause. Participants who were alive before final database lock or discontinuation of the study (discontinued study due to reasons other than death) were censored at their last known alive date on or before database lock. |
Countries
Australia, South Korea, United States
Participant flow
Recruitment details
This study was conducted at 15 study centers in Australia, South Korea, and the United States (US). A total of 119 participants were enrolled in the study and received ≥1 dose of study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Zanubrutinib and Obinutuzumab Part 1: Two dose regimens of zanubrutinib (320 mg QD and 160 mg BID) in combination with obinutuzumab (dose regimen consistent with the US prescribing information) were evaluated. Part 2: The 2 dose regimens selected from Part 1 (zanubrutinib 320 mg QD and 160 mg BID in combination with obinutuzumab) were investigated in 5 expansion cohorts. | 119 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 33 |
| Overall Study | Palliative care | 1 |
| Overall Study | Progressive disease at study withdrawal and death by end of study | 1 |
| Overall Study | Roll over to Long-Term Extension Study | 73 |
| Overall Study | Transitioned to Long Term Extension Study | 1 |
| Overall Study | Transitioned to Long Term Follow Up Study | 1 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Zanubrutinib and Obinutuzumab |
|---|---|
| Age, Continuous | 68 years |
| Body Mass Index | 26.876 kilograms/squared meter STANDARD_DEVIATION 4.9513 |
| Eastern Cooperative Oncology Group Grade 0 | 63 Participants |
| Eastern Cooperative Oncology Group Grade 1 | 48 Participants |
| Eastern Cooperative Oncology Group Grade 2 | 8 Participants |
| Height | 170.92 centimeters STANDARD_DEVIATION 9.382 |
| Pulse Rate | 78.2 beats/minute STANDARD_DEVIATION 13.86 |
| Race/Ethnicity, Customized Asian | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 117 Participants |
| Race/Ethnicity, Customized White | 107 Participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 78 Participants |
| Vital Signs Blood Pressure (Diastolic) | 71.5 millimeters of mercury STANDARD_DEVIATION 11.46 |
| Vital Signs Blood Pressure (Systolic) | 124.5 millimeters of mercury STANDARD_DEVIATION 17.75 |
| Weight | 78.95 kilograms STANDARD_DEVIATION 18.004 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 34 / 119 |
| other Total, other adverse events | 119 / 119 |
| serious Total, serious adverse events | 62 / 119 |
Outcome results
Primary
Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Partial Response
Partial response was defined as follows: * ≥ 50% reduction of serum IgM from baseline, * reduction in lymphadenopathy/splenomegaly (if present at baseline). For response assessments that occurred during cycles where a CT scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab. The Safety Analysis Set was the primary analysis set for the efficacy and safety analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Partial Response | 51 Participants |
Primary
Part 1: Number Of Deaths
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose: * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: Part 1: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Deaths | 0 Participants |
Primary
Part 1 : Number Of Participants Experiencing Adverse Events
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. A serious AE (SAE) was any untoward medical occurrence that, at any dose. * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: Part 1: Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 : Number Of Participants Experiencing Adverse Events | Any TEAE | 12 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 : Number Of Participants Experiencing Adverse Events | SAE | 7 Participants |
Primary
Part 1: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)
Dose-limiting toxicities were defined as a toxicity or AE occurring during the DLT assessment period (first 29 days of treatment), which is not clearly attributable to a cause other than zanubrutinib and/or obinutuzumab (such as disease progression, underlying illness, concurrent illness or concomitant medication) and meets one of the following criteria: * Grade 3 or 4 drug-related non-hematologic toxicity (excluding Grade 3 nausea, vomiting, hypertension, and asymptomatic laboratory abnormalities), * Grade 4 drug-related hematologic toxicity persisting for \>14 days, * any grade toxicity, which in the judgment of the investigator or Sponsor, required removal of the participant from the study.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: Part 1:The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Participants Experiencing Dose-limiting Toxicity (DLT) | 0 Participants |
Primary
Part 1: Number Of Participants With Clinical Laboratory Abnormalities
Laboratory results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.
Time frame: Day -28 to -1 (predose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Neutrophils: Low Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Lymphocytes: Low Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Phosphate: Low Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Lymphocytes: High Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Platelets: Low Directionality | 0 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Urate: High Directionality | 0 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Leukocytes: Low Directionality | 1 Participants |
| Part 1: 320 mg QD | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Urate: High Directionality | 1 Participants |
| Part 1: 320 mg QD | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Neutrophils: Low Directionality | 3 Participants |
| Part 1: 320 mg QD | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Platelets: Low Directionality | 1 Participants |
| Part 1: 320 mg QD | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Phosphate: Low Directionality | 0 Participants |
| Part 1: 320 mg QD | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Leukocytes: Low Directionality | 0 Participants |
| Part 1: 320 mg QD | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Lymphocytes: Low Directionality | 3 Participants |
| Part 1: 320 mg QD | Part 1: Number Of Participants With Clinical Laboratory Abnormalities | Lymphocytes: High Directionality | 1 Participants |
Secondary
Part 1 and Part 2: Duration Of Response (DOR)
Duration of response for responders was defined as the time (in months) from the date of the earliest qualifying response to the date of progressive disease or death due to any cause (whichever occurred earlier). Duration of response was analyzed using the same methods as the analysis for PFS. Responses after initiating new anticancer therapy, roll over to the long-term extension (LTE) study, or the first occurrence of disease progression were not considered in the analysis.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab. The Safety Analysis Set was the primary analysis set for the efficacy and safety analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Duration Of Response (DOR) | WM | 35.84 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Duration Of Response (DOR) | FL | 39.75 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Duration Of Response (DOR) | Non-GCB DLBCL | 12.75 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Duration Of Response (DOR) | CLL/SLL | NA Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Duration Of Response (DOR) | MCL | NA Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Duration Of Response (DOR) | MZL | NA Months |
Secondary
Part 1 and Part 2: Hematologic Improvement In Participants With CLL
The number and percentage of participants with CLL with anemia (hemoglobin ≤110 grams/liter \[g/L\]), neutropenia (absolute neutrophil count ≤1.5 x 10\^9/L), or thrombocytopenia (platelet count ≤100 x 10\^9/L) at baseline were estimated.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab. The Safety Analysis Set was the primary analysis set for the efficacy and safety analyses. Only participants with post-baseline assessments and available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Hematologic Improvement In Participants With CLL | Participants with anemia at baseline who had normalized hemoglobin after treatment | 11 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Hematologic Improvement In Participants With CLL | Participants with neutropenia at baseline who had normalized hemoglobin after treatment | 3 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Hematologic Improvement In Participants With CLL | Participants with thrombocytopenia at baseline who had normalized hemoglobin after treatment | 12 Participants |
Secondary
Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Complete Response
Complete response was defined as follows: * normal serum IgM values, * disappearance of monoclonal protein by immunofixation, * no histological evidence of bone marrow involvement, * complete resolution of lymphadenopathy/splenomegaly (if present at baseline) For response assessments that occurred during cycles where a computed tomography (CT) scan was not required, then results from prior scans (up to 12 weeks during the first 48 weeks and up to 24 weeks thereafter) could be carried forward in those participants with extramedullary disease at baseline.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab. The Safety Analysis Set was the primary analysis set for the efficacy and safety analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Complete Response | 36 Participants |
Secondary
Part 1 and Part 2: Overall Survival (OS)
Overall survival was defined as the time (in months) from the date of the start of the study treatment to death due to any cause. Participants who were alive before final database lock or discontinuation of the study (discontinued study due to reasons other than death) were censored at their last known alive date on or before database lock.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab. The Safety Analysis Set was the primary analysis set for the efficacy and safety analyses.. Only participants with post-baseline assessments and available data were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Overall Survival (OS) | Non-GCB DLBCL | 11.93 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Overall Survival (OS) | CLL/SLL | NA Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Overall Survival (OS) | WM | NA Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Overall Survival (OS) | FL | NA Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Overall Survival (OS) | MCL | NA Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Overall Survival (OS) | MZL | NA Months |
Secondary
Part 1 and Part 2: Progression-free Survival (PFS)
Progression-free survival was defined as time (in months) from the start of treatment with zanubrutinib or obinutuzumab to the first documented disease progression or death due to any cause, whichever occurred first. Results are reported as the median months for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL).
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab. The Safety Analysis Set was the primary analysis set for the efficacy and safety analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Progression-free Survival (PFS) | Non-GCB DLBCL | 2.86 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Progression-free Survival (PFS) | WM | 37.13 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Progression-free Survival (PFS) | FL | 24.87 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Progression-free Survival (PFS) | MZL | 40.25 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Progression-free Survival (PFS) | Total | 40.25 Months |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Progression-free Survival (PFS) | CLL/SLL | NA Months |
Secondary
Part 1 and Part 2: Steady State AUClast Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants in Part and Part 2, who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1.Only participants with available samples were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Steady State AUClast Of Zanubrutinib | 160 mg BID | 1074.1 nanogram/milliliter*hour | Geometric Coefficient of Variation 42.1 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Steady State AUClast Of Zanubrutinib | 320 mg QD | 2003.9 nanogram/milliliter*hour | Geometric Coefficient of Variation 42.6 |
Secondary
Part 1 and Part 2: Steady State Cmax of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants Part and Part 2 who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Steady State Cmax of Zanubrutinib | 160 mg BID | 328.5 nanogram/milliliter | Geometric Coefficient of Variation 52.3 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Steady State Cmax of Zanubrutinib | 320 mg QD | 580 nanogram/milliliter | Geometric Coefficient of Variation 42.6 |
Secondary
Part 1 and Part 2: Steady State Tmax Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants Part and Part 2 who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Steady State Tmax Of Zanubrutinib | 160 mg BID | 1.8 hour | Geometric Coefficient of Variation 67 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Steady State Tmax Of Zanubrutinib | 320 mg QD | 1.9 hour | Geometric Coefficient of Variation 48.4 |
Secondary
Part 1 and Part 2: Time To Response (TTR)
The TTR for responders was defined as time (in months) from the start of the study treatment to the date of the earliest qualifying response. The TTR was summarized using descriptive statistics. Responses after initiating new anticancer therapy, roll over to the LTE study, or the first occurrence of disease progression were not considered in the analysis of TTR.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab. The Safety Analysis Set was the primary analysis set for the efficacy and safety analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Time To Response (TTR) | Non-GCB DLBCL | 2.76 Months | Standard Deviation 0.297 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Time To Response (TTR) | Total | 3.18 Months | Standard Deviation 1.487 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Time To Response (TTR) | CLL/SLL | 3.14 Months | Standard Deviation 1.551 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Time To Response (TTR) | WM | 2.81 Months | Standard Deviation 0.05 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Time To Response (TTR) | FL | 3.32 Months | Standard Deviation 1.511 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Time To Response (TTR) | MCL | 2.77 Months | Standard Deviation 0.157 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1 and Part 2: Time To Response (TTR) | MZL | 5.62 Months | Standard Deviation 4.042 |
Secondary
Part 1: Apparent Clearance (CL/F) Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Apparent Clearance (CL/F) Of Zanubrutinib | 160 mg BID | 120789.1 milliliter/hour | Geometric Coefficient of Variation 60.965 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Apparent Clearance (CL/F) Of Zanubrutinib | 320 mg QD | 104832.9 milliliter/hour | Geometric Coefficient of Variation 33.681 |
Secondary
Part 1: Apparent Volume Of Distribution (Vz/F) Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Apparent Volume Of Distribution (Vz/F) Of Zanubrutinib | 160 mg BID | 327343.8 milliliter | Geometric Coefficient of Variation 97.981 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Apparent Volume Of Distribution (Vz/F) Of Zanubrutinib | 320 mg QD | 270810 milliliter | Geometric Coefficient of Variation 36.099 |
Secondary
Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To Infinity Time (AUC) Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To Infinity Time (AUC) Of Zanubrutinib | 160 mg BID | 1324.63 nanogram/milliliter*hour | Geometric Coefficient of Variation 60.981 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To Infinity Time (AUC) Of Zanubrutinib | 320 mg QD | 3052.47 nanogram/milliliter*hour | Geometric Coefficient of Variation 33.681 |
Secondary
Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUClast) Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The Pharmacokinetic Analysis Set included all participants who received at least the first administration of zanubrutinib and provided PK samples per protocol after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUClast) Of Zanubrutinib | 160 mg BID | 1123.59 nanogram/milliliter*hour | Geometric Coefficient of Variation 71.482 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUClast) Of Zanubrutinib | 320 mg QD | 2179.54 nanogram/milliliter*hour | Geometric Coefficient of Variation 70.237 |
Secondary
Part 1: Maximum Plasma Concentration (Cmax) Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Maximum Plasma Concentration (Cmax) Of Zanubrutinib | 160 mg BID | 360.42 nanogram/milliliter | Geometric Coefficient of Variation 90.35 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Maximum Plasma Concentration (Cmax) Of Zanubrutinib | 320 mg QD | 589.37 nanogram/milliliter | Geometric Coefficient of Variation 79.884 |
Secondary
Part 1: Terminal Elimination Half-life (t1/2) Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Terminal Elimination Half-life (t1/2) Of Zanubrutinib | 160 mg BID | 1.88 hour | Geometric Coefficient of Variation 29.532 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Terminal Elimination Half-life (t1/2) Of Zanubrutinib | 320 mg QD | 1.79 hour | Geometric Coefficient of Variation 19.945 |
Secondary
Part 1: Time To Maximum Plasma Concentration (Tmax) Of Zanubrutinib
Time frame: Day 1 Cycle 1, Predose (within 3 hours), hours 1, 2, 4 and 7
Population: The PK Analysis Set included all participants who received at least the first administration of zanubrutinib and provided PK samples per protocol (without any significant protocol deviation affecting the PK blood sample) after the first administration of zanubrutinib on Cycle 1 Day 1. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Time To Maximum Plasma Concentration (Tmax) Of Zanubrutinib | 160 mg BID | 1.60 hour | Geometric Coefficient of Variation 38.285 |
| Part 1: Zanubrutinib and Obinutuzumab | Part 1: Time To Maximum Plasma Concentration (Tmax) Of Zanubrutinib | 320 mg QD | 1.73 hour | Geometric Coefficient of Variation 88.663 |
Secondary
Part 2: Number Of Deaths
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose,: * resulted in death, * is life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Road traffic accident | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Bone marrow failure and metastatic skin squamous cell carcinoma | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Cardiac arrest during admission to private hospital for bowel resection for colorectal cancer | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Chest infection | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | CLL/sepsis | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Metastatic breast cancer | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Undisclosed | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Progression of disease | 24 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Total deaths | 34 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Unknown | 2 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Deaths | Acute respiratory distress syndrome | 1 Participants |
Secondary
Part 2: Number Of Participants Experiencing Adverse Events
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product (zanubrutinib in combination with obinutuzumab). An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. An SAE was any untoward medical occurrence that, at any dose,: * resulted in death, * was life threatening, * required hospitalization or prolongation of existing hospitalization, * resulted in disability/incapacity, * was a congenital anomaly/birth defect.
Time frame: Day 1 (first dose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants Experiencing Adverse Events | Any AE | 119 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants Experiencing Adverse Events | SAE | 62 Participants |
Secondary
Part 2: Number Of Participants With Clinical Laboratory Abnormalities
Results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.
Time frame: Day -28 to -1 (predose) through 4 years and 8 months
Population: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Lymphocytes: High Directionality | 2 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Neutrophils: Low Directionality | 11 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Platelets: Low Directionality | 7 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Alanine Aminotransferase: High Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Albumin: Low Directionality | 5 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Alkaline Phosphatase: High Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Aspartate Aminotransferase: High Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Glucose: High Directionality | 3 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Phosphate: Low Directionality | 3 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Sodium: Low Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Urate: High Directionality | 1 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Hemoglobin: Low Directionality | 3 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Leukocytes: Low Directionality | 7 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Leukocytes: High Directionality | 0 Participants |
| Part 1: Zanubrutinib and Obinutuzumab | Part 2: Number Of Participants With Clinical Laboratory Abnormalities | Lymphocytes: Low Directionality | 10 Participants |