Trial Outcomes & Findings for Zanubrutinib (BGB-3111) in Combination With Tislelizumab (BGB-A317) in Participants With B-cell Malignancies (NCT NCT02795182)

Last Updated: 2022-07-01

Results Overview

The MTD of tislelizumab is considered the dose level below that at which at least 2 participants (or at least 33%) experience a dose-limiting toxicity (DLT).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

75 participants

Primary outcome timeframe

From the date of first dose of study drugs until RP2D was determined (Approximately 1 year and 10 months)

Results posted on

2022-07-01

Participant Flow

The study consisted of a dose escalation phase during which 3 dose levels of tislelizumab were administered in combination with a total of 320 mg zanubrutinib to determine the recommended phase 2 dose (RP2D). Once RP2D was determined all participants remaining in the study were switched to RP2D. A total of 75 participants were enrolled in both phases combined. As pre-specified in the protocol, analyses were conducted by disease subtype on the overall enrolled participants and not by phases.

Participant milestones

Participant milestones
Measure	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg Q3W Zanubrutinib 320 mg once daily (QD) orally with tislelizumab 2.0 milligrams/kilogram (mg/kg) intravenously (IV) once every 3 weeks until unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W Zanubrutinib 160 mg twice daily (BID) orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Overall Study STARTED	15	10	7	43
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	15	10	7	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg Q3W Zanubrutinib 320 mg once daily (QD) orally with tislelizumab 2.0 milligrams/kilogram (mg/kg) intravenously (IV) once every 3 weeks until unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W Zanubrutinib 160 mg twice daily (BID) orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Overall Study Death	5	4	4	18
Overall Study Sponsor's Decision at Discontinuation and Death at End of Trial	0	0	0	1
Overall Study Physician's decision at Discontinuation and Death at End of Trial	0	0	0	2
Overall Study Study Ended by Sponsor Once Primary and Secondary Objectives Were Met	3	2	0	8
Overall Study Withdrawal by Subject	4	0	0	3
Overall Study Lost to Follow-up	0	0	1	1
Overall Study Roll Over to Long Term Extension	3	3	2	5
Overall Study Progressive Disease	0	1	0	4
Overall Study Physician Decision	0	0	0	1

Baseline Characteristics

Zanubrutinib (BGB-3111) in Combination With Tislelizumab (BGB-A317) in Participants With B-cell Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg Q3W n=15 Participants Zanubrutinib 320 mg QD orally with tislelizumab 2.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W n=10 Participants Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=7 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=43 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Total n=75 Participants Total of all reporting groups
Age, Continuous	60.4 years STANDARD_DEVIATION 12.63 • n=39 Participants	60.7 years STANDARD_DEVIATION 6.52 • n=41 Participants	70.4 years STANDARD_DEVIATION 5.26 • n=35 Participants	66.7 years STANDARD_DEVIATION 9.85 • n=31 Participants	65.0 years STANDARD_DEVIATION 10.20 • n=146 Participants
Sex: Female, Male Female	4 Participants n=39 Participants	5 Participants n=41 Participants	4 Participants n=35 Participants	16 Participants n=31 Participants	29 Participants n=146 Participants
Sex: Female, Male Male	11 Participants n=39 Participants	5 Participants n=41 Participants	3 Participants n=35 Participants	27 Participants n=31 Participants	46 Participants n=146 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	1 Participants n=31 Participants	1 Participants n=146 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=39 Participants	7 Participants n=41 Participants	7 Participants n=35 Participants	38 Participants n=31 Participants	64 Participants n=146 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=39 Participants	3 Participants n=41 Participants	0 Participants n=35 Participants	4 Participants n=31 Participants	10 Participants n=146 Participants
Race/Ethnicity, Customized Race- White	14 Participants n=39 Participants	9 Participants n=41 Participants	7 Participants n=35 Participants	33 Participants n=31 Participants	63 Participants n=146 Participants
Race/Ethnicity, Customized Race - Asian	1 Participants n=39 Participants	1 Participants n=41 Participants	0 Participants n=35 Participants	9 Participants n=31 Participants	11 Participants n=146 Participants
Race/Ethnicity, Customized Race - Other	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	1 Participants n=31 Participants	1 Participants n=146 Participants

PRIMARY outcome

Timeframe: From the date of first dose of study drugs until RP2D was determined (Approximately 1 year and 10 months)

Population: Dose Escalation Phase: Safety analysis set: Includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab.

The MTD of tislelizumab is considered the dose level below that at which at least 2 participants (or at least 33%) experience a dose-limiting toxicity (DLT).

Outcome measures

Outcome measures
Measure	Dose Escalation Phase n=32 Participants Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Transformed Lymphoid Malignancy Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	PCNSL or SCNSL of Breast or Testicular Origin Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Dose Escalation: Maximum Tolerated Dose (MTD) of Tislelizumab	NA mg MTD not reached because number of participants with dose limiting toxicities (DLTs) per dose level did not reach the required threshold.	—	—	—	—	—

PRIMARY outcome

Timeframe: From the date of first dose of study drugs until final R2PD was decided (Approximately 1 year and 10 months)

Population: Dose Escalation Phase: Safety analysis set: Included all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab.

The RP2D of tislelizumab in combination with zanubrutinib will be selected by taking into account the safety, tolerability, and pharmacokinetic (PK) profile.

Outcome measures

Outcome measures
Measure	Dose Escalation Phase n=32 Participants Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Transformed Lymphoid Malignancy Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	PCNSL or SCNSL of Breast or Testicular Origin Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Dose Escalation: RP2D of Tislelizumab	200 mg	—	—	—	—	—

SECONDARY outcome

Timeframe: From the day of first dose of study drug until end of study (up to 4 years and 6 months)

Population: Safety Analysis Set

A treatment-emergent adverse event (TEAE) was defined as an AE that had an onset date during the treatment emergent period, defined as from the first dose date of zanubrutinib or tislelizumab (whichever is earlier) through 30 days after the last dose (permanent discontinuation of study drug) of zanubrutinib or 90 days after the last dose of tislelizumab, whichever is later, or prior to initiation of new anti-cancer therapy. Treatment-related serious adverse events (SAEs) and any worsening of a TEAE by PT post treatment-emergent period were also counted as TEAEs.

Outcome measures

Outcome measures
Measure	Dose Escalation Phase n=15 Participants Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W n=10 Participants Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=7 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=43 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Transformed Lymphoid Malignancy Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	PCNSL or SCNSL of Breast or Testicular Origin Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Number of Participants With TEAEs and SAEs Participants With at Least One TEAE	15 Number of participants	9 Number of participants	7 Number of participants	40 Number of participants	—	—
Number of Participants With TEAEs and SAEs Participants With at Least One SAE	10 Number of participants	10 Number of participants	4 Number of participants	23 Number of participants	—	—

SECONDARY outcome

Timeframe: Up to 4 years and 6 months

Population: Safety analysis set : Includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab. Per protocol Safety analysis set was used for all safety and efficacy outcome analyses. All efficacy analyses were done by disease type for both part 1 and part 2 combined and not by dose level as specified in the protocol.

ORR, is defined as the percentage of participants who had complete response (CR) or partial response (PR) by standard disease-specific response criteria. for WM participants ORR includes minor response (MR) and very good partial response (VGPR).

Outcome measures

Outcome measures
Measure	Dose Escalation Phase n=16 Participants Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W n=12 Participants Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=15 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=7 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Transformed Lymphoid Malignancy n=20 Participants Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	PCNSL or SCNSL of Breast or Testicular Origin n=5 Participants Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Overall Response Rate	37.5 Percentage of participants Interval 15.2 to 64.6	25.0 Percentage of participants Interval 5.5 to 57.2	40.0 Percentage of participants Interval 16.3 to 67.7	42.9 Percentage of participants Interval 9.9 to 81.6	40 Percentage of participants Interval 19.1 to 63.9	40 Percentage of participants Interval 5.3 to 85.3

SECONDARY outcome

Timeframe: Up to 4 years and 6 months

DOR is defined as the time from the date that a confirmed objective response is first documented to the date of progressive disease (PD) or death due to any cause for those participants with a confirmed PR or CR.

Outcome measures

Outcome measures
Measure	Dose Escalation Phase n=16 Participants Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W n=12 Participants Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=15 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=7 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Transformed Lymphoid Malignancy n=20 Participants Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	PCNSL or SCNSL of Breast or Testicular Origin n=5 Participants Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Duration of Response (DOR)	22.36 Months Interval 7.72 to NA = Not estimable due to insufficient number of participants with events	NA Months NA = Not estimable due to insufficient number of participants with events	6.79 Months Interval 2.36 to NA = Not estimable due to insufficient number of participants with events	17.47 Months Interval 2.96 to NA = Not estimable due to insufficient number of participants with events	8.89 Months Interval 2.83 to NA = Not estimable due to insufficient number of participants with events	7.80 Months Interval 7.06 to 8.55

SECONDARY outcome

Timeframe: Up to 4 years and 6 months

PFS, is defined as the time from the first dose of study medication to objective disease progression or death

Outcome measures

Outcome measures
Measure	Dose Escalation Phase n=16 Participants Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W n=12 Participants Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=15 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=7 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Transformed Lymphoid Malignancy n=20 Participants Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	PCNSL or SCNSL of Breast or Testicular Origin n=5 Participants Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Progression Free Survival (PFS)	16.94 Months Interval 5.39 to NA = Not estimable due to insufficient number of participants with events	1.43 Months Interval 0.57 to NA = Not estimable due to insufficient number of participants with events	2.80 Months Interval 1.43 to 6.99	2.93 Months Interval 2.43 to 20.33	4.68 Months Interval 1.26 to 8.52	8.42 Months Interval 0.33 to 16.07

SECONDARY outcome

Timeframe: From the day of first dose of study drug until end of study (up to 4 years and 6 months)

Population: Safety analysis set included all participants who received at least 1 dose of tislelizumab. N is the number of evaluable participants. Evaluable participants received at least one complete dose of Tislelizumab and for whom one baseline ADA and at least one post dose ADA values are available.

Outcome measures

Outcome measures
Measure	Dose Escalation Phase n=3 Participants Participants received either zanubrutinib 320 mg once daily orally in combination with tislelizumab 2.0 mg/kg IV once every 3 weeks, or zanubrutinib 320 mg once daily orally with tislelizumab 5.0 mg/kg IV once every 3 weeks or zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks unresolved toxicity, unacceptable adverse events (AEs) or discontinuation by sponsor	Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W n=4 Participants Zanubrutinib 320 mg QD orally with tislelizumab 5.0 mg/kg IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor.	Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=5 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W n=35 Participants Zanubrutinib 160 mg BID orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	Transformed Lymphoid Malignancy Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor	PCNSL or SCNSL of Breast or Testicular Origin Zanubrutinib 160 mg twice daily orally with tislelizumab 200 mg flat dose IV once every 3 weeks until unresolved toxicity, unacceptable AEs or discontinuation by sponsor
Number of Participants With Anti-Drug Antibodies (ADAs) to Tislelizumab Treatment Emergent ADA	0 Number of participants	0 Number of participants	0 Number of participants	1 Number of participants	—	—
Number of Participants With Anti-Drug Antibodies (ADAs) to Tislelizumab Neutralizing antibody Positive	0 Number of participants	0 Number of participants	0 Number of participants	0 Number of participants	—	—

Adverse Events

Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg

Serious events: 10 serious events

Other events: 15 other events

Deaths: 5 deaths

Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg

Serious events: 10 serious events

Other events: 9 other events

Deaths: 4 deaths

Dose Escalation: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W

Serious events: 4 serious events

Other events: 7 other events

Deaths: 4 deaths

Dose Expansion: Zanubrutinib 160 mg BID + Tislelizumab 200 mg Flat Q3W

Serious events: 23 serious events

Other events: 40 other events

Deaths: 21 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

BeiGene

Phone: +1-877-828-5568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
Publication restrictions are in place

Restriction type: OTHER