A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies

Number of participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) including results from laboratory assessments, electrocardiograms (ECGs), and physical examinations, and that meet protocol-defined dose-limiting toxicities (DLTs); as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.

MTD is defined as the highest evaluated dose with an estimated toxicity rate closest to the target, while MAD is the highest dose given if MTD is not reached.

RDFE of BGB-16673 alone will be determined based upon the MTD or MAD.

Defined as the percentage of participants achieving a best overall response of partial response (PR) or better, assessed by the Independent Review Committee for participants with R/R CLL/SLL and R/R WM (in participants with WM, this is also referred to as major response rate) and by the investigator for other cohorts (R/R MCL, R/R MZL, R/R FL, R/R non-GCB DLBCL, R/R Richter's transformation to DLBCL), evaluated using the Lugano criteria for NHL and SLL, International Workshop of Chronic Lymphocytic Leukemia (iwCLL) criteria for CLL, and the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) criteria for WM.

Defined as the percentage of participants whose best overall response is partial response or better, as assessed by the investigator and evaluated according to the following criteria: the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for R/R CLL, the International Workshop on Waldenström's Macroglobulinemia (IWWM-11) criteria for R/R WM (in participants with WM, this is also referred to as major response rate), and the Lugano criteria for R/R NHL.

Defined as the percentage of participants with R/R CLL/SLL whose best overall response is better than stable disease, as determined by investigators.

Defined as the percentage of participants with R/R WM who have a response rate of minor response or better.

Number of Japanese participants in Part 1e with TEAEs and SAEs, including results from laboratory assessments, ECGs, and physical examinations, that meet protocol-defined DLTs, graded according to the NCI-CTCAE v5.0.

The Recommended Phase 2 Dose (RP2D) is determined by the sponsor based on the Safety Monitoring Committee's recommendations, taking into account the overall clinical safety, efficacy, pharmacokinetic (PK), and pharmacodynamic data.

Number of participants with TEAEs and SAEs, including results from laboratory assessments, ECGs, and physical examinations, graded according to the NCI-CTCAE v5.0.

Defined as the percentage of participants with CLL/SLL with a best overall response of PR or better, as determined by investigators.

Defined as the percentage of participants with WM whose best overall response is PR or better, as determined by investigators using the IWWM-11 criteria.

Defined as the percentage of participants who achieve at least a minor response (MR) or a more favorable outcome, as assessed by investigators for participants with R/R WM.

Defined as the percentage of participants with R/R WM with best response of VGPR or better as determined by IRC and investigator.

Defined as the percentage of participants with R/R CLL/SLL whose best overall response is better than stable disease, as determined by IRC and investigator.

DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is documented or death, whichever comes first as assessed by the investigator and the IRC.

TTOR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better), as assessed by IRC and the investigator

Defined as the time from the date of treatment initiation to the date of first response of PR or better in participants with R/R WM.

Defined as the time to first response based on best overall response of better than stable disease, per IRC and investigator.

Defined as the time to first response based on best overall response of minor response or better, per IRC and investigator.

Defined as the time from the treatment start date to the initiation of subsequent anticancer therapy.

PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by IRC for R/R CLL/SLL and R/R WM and by the investigator for all participants.

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

Mean change from baseline in the 'physical well-being' and 'functional well-being' subscales of the FACT-Leu for participants with R/R CLL/SLL. FACT-Leu is a 44-item PRO questionnaire with five subscales used to measure health-related quality of life (HRQoL) in leukemia patients.

Mean change from baseline in the NFlymSI-18 subscales of disease-related symptoms (DRSP) and 'treatment side effects' for participants with R/R MCL and participants with R/R WM. The NFlymSI-18 is an 18-item patient-reported outcome (PRO) tool specifically designed to assess symptoms and treatment impacts in patients with non-Hodgkin lymphoma.