Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Leukemia

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Obinutuzumab

Zanubrutinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

In the dose-escalation part, dose levels and regimens were evaluated. In the indication-specific expansion cohorts, participants were assigned to different cohorts based on histology type.

Study Director

This study evaluated the safety and preliminary efficacy of BGB-3111 (zanubrutinib) in combination with obinutuzumab in participants with B-cell lymphoid malignancies.

BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid Malignancies

A Phase 1b Study to Assess Safety, Tolerability and Antitumor Activity of the Combination of BGB 3111 With Obinutuzumab in Subjects With B-Cell Lymphoid Malignancies

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.

Laboratory results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

Results are reported as participants with shifts towards (high directionality) or away (low directionality) from Grade 3 or Higher Toxicity.

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.

BeiGene

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.

Zanubrutinib and Obinutuzumab

Age, Continuous

Sex: Female, Male

White

Black or African American

Asian

Not Hispanic or Latino

Hispanic or Latino

Race/Ethnicity, Customized

Blood Pressure (Systolic)

Blood Pressure (Diastolic)

Vital Signs

Pulse Rate

Weight

Height

Body Mass Index

Grade 0

Grade 1

Grade 2

Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work; Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; Grade 0 was considered to be the best outcome.

Eastern Cooperative Oncology Group

Any TEAE

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 1: Zanubrutinib and Obinutuzumab

Part 1: Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab

Part 1 : Number Of Participants Experiencing Adverse Events

Leukocytes: Low Directionality

Lymphocytes: Low Directionality

Lymphocytes: High Directionality

Neutrophils: Low Directionality

Platelets: Low Directionality

Phosphate: Low Directionality

Urate: High Directionality

Part 1: 160 mg BID

Part 1: 320 mg QD

The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab

Part 1: Number Of Participants With Clinical Laboratory Abnormalities

Part 1: The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab

Part 1: Number Of Deaths

Part 1:The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab

Part 1: Number Of Participants Experiencing Dose-limiting Toxicity (DLT)

Part 1: Two dose regimens of zanubrutinib (320 milligrams \[mg\] once daily \[QD\] and 160 mg twice daily \[BID\]) 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.

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.

Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Partial Response

Part 1 and Part 2: Number Of Participants Achieving A Best Response Of Complete Response

Non-GCB DLBCL

Total

CLL/SLL

Part 1 and Part 2: Progression-free Survival (PFS)

Part 1 and Part 2: Duration Of Response (DOR)

Part 1 and Part 2: Time To Response (TTR)

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.

Part 1 and Part 2: Overall Survival (OS)

Participants with anemia at baseline who had normalized hemoglobin after treatment

Participants with neutropenia at baseline who had normalized hemoglobin after treatment

Participants with thrombocytopenia at baseline who had normalized hemoglobin after treatment

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.

Part 1 and Part 2: Hematologic Improvement In Participants With CLL

160 mg BID

320 mg QD

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.

Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To The Time Of The Last Measurable Concentration (AUClast) Of Zanubrutinib

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.

Part 1: Area Under The Plasma Concentration-time Curve From Time 0 To Infinity Time (AUC) Of Zanubrutinib

Part 1: Maximum Plasma Concentration (Cmax) Of Zanubrutinib

Part 1: Time To Maximum Plasma Concentration (Tmax) Of Zanubrutinib

Part 1: Terminal Elimination Half-life (t1/2) Of Zanubrutinib

Part 1: Apparent Clearance (CL/F) Of Zanubrutinib

Part 1: Apparent Volume Of Distribution (Vz/F) Of Zanubrutinib

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.

Part 1 and Part 2: Steady State AUClast Of Zanubrutinib

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.

Part 1 and Part 2: Steady State Cmax of Zanubrutinib

Part 1 and Part 2: Steady State Tmax Of Zanubrutinib

Any AE

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.

Part 2: Zanubrutinib and Obinutuzumab

The Safety Analysis Set included all participants who received ≥ 1 dose of zanubrutinib and/or obinutuzumab.

Part 2: Number Of Participants Experiencing Adverse Events

Hemoglobin: Low Directionality

Leukocytes: High Directionality

Alanine Aminotransferase: High Directionality

Albumin: Low Directionality

Alkaline Phosphatase: High Directionality

Aspartate Aminotransferase: High Directionality

Glucose: High Directionality

Sodium: Low Directionality

Part 2: 160 mg BID

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.

Spots Global Cancer Trial Database for BGB 3111 in Combination With Obinutuzumab in Participants With B-Cell Lymphoid Malignancies

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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