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1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) with adverse events leading to discontinuation, and Adverse Events (AEs) graded according NCI-CTCAE V5. (Time Frame - approximately 3 years): 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 the first dose of the study drug and up to 30 days after the last dose of study treatment or the initiation of a new anticancer therapy, whichever is earlier
2. Recommended Phase 2 Dose (RP2D) of BGB-16673 (Time Frame - approximately 3 years): RP2D is the recommended dose for further evaluation in Part 2, determined based on the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data in Part 1.
3. Maximum Tolerated Dose (MTD) of BGB-16673 (Time Frame - approximately 3 years): determined by the sponsor based on the Safety Monitoring Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data
4. Phase 2: Overall response rate (ORR) (Time Frame - approximately 3 years): Cohort specific ORRs based on best overall response of partial response (PR) or better as assessed by Independent Review Committee (IRC) for prticipants in cohorts 1 and 2; by investigator for other cohorts.
Secondary outcome:
1. Single Dose Maximum observed plasma concentration (Cmax) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
2. Single Dose Minimum observed plasma concentration (Cmin) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
3. Single Dose Time to reach Cmax (tmax) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
4. Single Dose Time to reach half of Cmax (T1/2) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
5. Single Dose Area under the plasma concentration-time curve (AUC) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
6. Single Dose apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
7. Single Dose apparent volume of distribution (Vz/F) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
8. Single Dose accumulation ratios of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
9. Steady State Maximum observed plasma concentration (Cmax) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
10. Steady State minimum observed plasma concentration (Cmin) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
11. Steady State Time to reach Cmax (tmax) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
12. Steady State Time to reach half of Cmax (T1/2) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
13. Steady State Area under the plasma concentration-time curve (AUC) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
14. Steady State apparent total clearance of drug from plasma after oral administration (CL/F) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
15. Steady State apparent volume of distribution (Vz/F) of BGB-16673 (Time Frame - Day 1 pre-dose and 2, 4, 6,8,24, 48 and 72 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
16. Bruton's tyrosine kinase (BTK) protein degradation in peripheral blood after BGB-16673 monotherapy (Time Frame - Day 1 pre-dose and 8 hours post-dose (approximately 2 years)): Collected for both Part 1 and Part 2
17. Phase 1: Overall response rate (ORR) (Time Frame - approximately 3 years): defined as the proportion of participants whose best overall response is better than stable disease.
18. Phase 1: Number of Waldenström Macroglobulinemia (WM) Participants with major response rate (MRR) (Time Frame - approximately 3 years): MRR is defined as the proportion of participants whose best overall response (BOR) is partial response (PR) or better (PR, very good partial response (VGPR), or complete response (CR)).
19. Phase 2: Duration of Response (DOR) (Time Frame - approximately 3 years): DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented or death, whichever comes first as assessed by the investigator and the IRC.
20. Phase 2: Time to Response (TTR) (Time Frame - approximately 3 years): TTR 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
21. Phase 2: Progression- Free Survival (PFS) (Time Frame - approximately 3 years): PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by IRC and the investigator
22. Phase 2: Overall Survival (OS) (Time Frame - approximately 3 years): OS is defined as the time from first study drug administration to the date of death due to any cause
23. Phase 2 (Cohort 1): Best Overall Response (BOR) of partial response with lymphocytosis or better (Time Frame - approximately 3 years): Best overall response is defined as the best response recorded from the first dose of the study drug until the data cutoff date or initiation of a new anticancer treatment, whichever occurs first. As determined by IRC and investigators.
24. Phase 2 (Cohort 3): BOR of minor response or better (Time Frame - approximately 3 years)
25. Phase 2 (Cohort 1): Participant-reported outcomes (PRO) via Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) questionarre (Time Frame - approximately 3 years): FACT-Leu is a PRO questionnaire that is developed to measure disease-specific symptoms and/or treatment-related concerns in participants with leukemia (Cela et al. 2012). It has been linguistically validated in over 50 languages, and frequently to measure HRQoL in chronic lymphocytic leukemia (CLL) participants.
The questionnaire is comprised of 44 questions and 5 subscales including Physical Well-being (7 items), Social / Family Well-being (7 items), Emotional Well-being (6 items), Functional Wellbeing (7 items), and 17 single items under Additional Concerns).
26. Phase 2 (Cohort 2): Participant-reported outcomes (PRO) via National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 (NFLymSI-18) (Time Frame - approximately 3 years): The NFlymSI-18 is a participant-reported outcome questionnaire that is developed to measure disease-specific symptoms and/or treatment-related concerns in participants with advanced lymphoma
Experimental: Part 1a (Monotherapy Dose Escalation) Dose escalation in selected R/R B-Cell malignancies to inform safety, tolerability and MTD.
Experimental: Part 1b (Monotherapy Safety Expansion) Additional participants with selected R/R B-Cell malignancies will be enrolled at selected doses to help inform the selection of the recommended phase two dose (RP2D).
Experimental: Part 1c (Additional Monotherapy Safety Expansion) After RP2D is determined, additional safety data will be collected to confirm RP2D for participants with selected B-cell malignancies not being evaluated in Part 2
Experimental: Part 2 (Monotherapy Expansion) The totality of the data from Part 1a, Part 1b, and Part 1c will be used to further evaluate the safety and efficacy of BGB-16673 at the recommended dose(s) for Phase 2 expansion in specific histologies.
