Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Zanubrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants were administered up to 320 mg total daily dose of zanubrutinib until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up

Study Director

This study evaluated the safety, tolerability, pharmacokinetic profile and efficacy of BGB-3111 in participants with B-cell lymphoid malignancies.

Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies

A Phase I/II, Open-Label, Multiple-Dose, Dose Escalation and Expansion Study to Investigate the Safety and Pharmacokinetics of the BTK Inhibitor BGB-3111 in Subjects With B-Cell Lymphoid Malignancies

Number of participants with adverse events and serious adverse events, including clinically relevant physical examinations and laboratory measurements

RP2D for zanubrutinib was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 320 mg QD

ORR is defined as the percentage of participants with partial or complete response (CR), as assessed by the investigator. For CLL/SLL, ORR includes partial response (PR) with lymphocytosis (PR-L) or better (includes PR-L, PR, nodular PR or nPR and CR with incomplete marrow recovery or CRi) and for MW, ORR includes minor response or better. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

CRR is defined as the percentage of participants who achieve a complete response, as assessed by the investigator. For CLL/SLL, CRR includes CRi or better. For WM, CRR includes very good partial response (VGPR) or better. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

PR or better is defined as the percentage of participants who achieve a partial response or better, as assessed by the investigator. For CLL/SLL, includes PR, nPR, CRi, CR and for WM includes PR, VGPR, and CR. Efficacy results are reported for the B-cell malignancy subtypes chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Waldenström macroglobulinemia (WM).

PFS is defined as the time from the first dose date of study drug to the date of the earliest occurrence of progressive disease or death due to any cause, whichever occurs first. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

OS is defined as the time from the date of the first dose to death due to any cause. Efficacy results are reported for each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

DOR for responders is defined as time from the date of the earliest qualifying response to the date of progressive disease or death for any cause, whichever occurs earlier. Efficacy results are reported for responders (defined as PR or better, except CLL/SLL and WM) in each of the B-cell malignancy subtypes: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; PR with lymphocytosis or better), Waldenstrom macroglobulinemia (WM; minor response or better), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Richter's Transformation (RT), and Hairy cell leukemia (HCL).

Number of participants with greater than 75% BTK occupancy of zanubrutinib in peripheral blood mononuclear cells (PBMCs)

BeiGene

One participant in the 320 mg QD group discontinued the study for Other reasons, as shown in the participant flow section, and subsequently died after study discontinuation. That participant is counted under all-cause mortality in this section.

Participants received 40 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up

Part 1: 40 mg QD

Participants received 80 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up

Part 1: 80 mg QD

Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up

Part 1: 160 mg QD

Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.

Part 1 and Part 2: 160 mg BID

Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.

Part 1 and Part 2: 320 mg QD

Part 1: Participants received 160 mg of zanubrutinib twice daily (BID) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up were evaluated. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.

Part 1: Participants received 320 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to follow-up were evaluated. Part 2: This dose regimen was selected for further evaluation in various expansion cohorts that span multiple disease types.

Total

Age, Continuous

Sex: Female, Male

White

Asian

Black or African American

Native Hawaiians or other Pacific Islanders

Multiple

Not Reported

Other

Race/Ethnicity, Customized

The Safety Analysis Set included all participants who received ≥ 1 dose of study drug

At least one treatment-emergent adverse event

Serious adverse events

Parts 1 and 2: 160 mg BID

Parts 1 and 2: 320 mg QD

Part 1 and Part 2: Number of Participants With Adverse Events

Five dose regimens of zanubrutinib (40 mg QD, 80 mg QD, 160 mg QD, 160 mg BID, and 320 mg QD) were evaluated.

Part 1: Zanubrutinib

Part 1: Recommended Phase 2 Dose (RP2D) for Zanubrutinib

The pharmacokinetic (PK) analysis set included all participants for whom valid zanubrutinib PK parameters could be estimated, shown as overall number analyzed. Only participants with available data per dose were included in the analysis.

Part 1 and Part 2: Area Under the Curve From Time 0 to the Last Sampling Time Point Within the Dose Interval (AUClast) of Zanubrutinib

The PK analysis set included all participants for whom valid zanubrutinib PK parameters could be estimated, shown as overall number analyzed. Only participants with available data per dose were included in the analysis.

Part 1 and Part 2: Area Under the Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Zanubrutinib

Participants received 160 mg of zanubrutinib once daily (QD) orally until disease progression, intolerance or death, withdrawal of consent, or loss to

Part 1 and Part 2: Maximum Observed Plasma Concentration (Cmax) After Administration of Zanubrutinib

Part 1 and Part 2: Time to Maximum Observed Plasma Concentration (Tmax) of Zanubrutinib

Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Zanubrutinib

Part 1 and Part 2: Apparent Clearance (CL/F) of Zanubrutinib

Part 1 and Part 2: Apparent Volume of Distribution of Zanubrutinib During the Terminal Phase (Vz/F)

CLL/SLL

DLBCL

The dose regimens from Part 1 (40 mg, 80 mg, 160 mg QD, 160 mg BID and 320 mg QD) and Part 2 (160 mg BID and 320 mg QD) were evaluated in different disease types. Efficacy evaluations are reported by disease type for Parts 1 and 2 combined, as pre-specified in the statistical analysis plan.

Part 1 and Part 2: Overall

Efficacy Evaluable Set consists of all participants who received at least one dose of zanubrutinib; for WM, participants also must have a baseline IgM (or M-protein) ≥ 5 g/L and no prior exposure to a BTK inhibitor.

Part 1 and Part 2: Overall Response Rate (ORR)

Part 1 and Part 2: Complete Response Rate (CRR)

Part 1 and Part 2: Partial Response (PR) or Better

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

Part 1 and Part 2: Overall Survival (OS)

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

Pharmacodynamic analysis set consisted of participants in which PBMCs were collected and evaluable samples were obtained.

Spots Global Cancer Trial Database for Study of the Safety and Pharmacokinetics of BGB-3111 in Subjects With B-Cell Lymphoid Malignancies

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

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