Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Leukemia

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Tislelizumab

Zanubrutinib

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Based on results of the dose escalation cohorts and the identified recommended Phase 2 dose, all patients will receive zanubrutinib at 160 mg orally twice daily in combination with intravenous infusion of tislelizumab 200mg given every 21 days, to be continued until disease progression, unacceptable toxicity, treatment consent withdrawal, or study termination

Study Director

This study is evaluating the safety and preliminary efficacy of BGB-3111 in combination with BGB-A317 in participants with B-cell lymphoid malignancies.

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

A Phase 1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Assess Safety, Tolerability and Antitumor Activities of the Combination of BGB-3111 With BGB-A317 in Subjects With B-Cell Lymphoid Malignancies

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).

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

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.

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).

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.

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

BeiGene

Safety analysis set: Includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab

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 2.0 mg/kg

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 320 mg QD + Tislelizumab 5.0 mg/kg

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

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

Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 2.0 mg/kg Q3W

Dose Escalation: Zanubrutinib 320 mg QD + Tislelizumab 5.0 mg/kg Q3W

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race- White

Race - Asian

Race - Other

Race/Ethnicity, Customized

Safety analysis set includes all participants who receive at least 1 dose of zanubrutinib and/or tislelizumab.

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 Phase

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

Dose Escalation: Maximum Tolerated Dose (MTD) of Tislelizumab

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

Dose Escalation: RP2D of Tislelizumab

Participants With at Least One TEAE

Participants With at Least One SAE

Number of Participants With TEAEs and SAEs

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. This group included participants with CLL/SLL, WM, FL, MCL and MZL.

Other B-Cell Malignancies

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

GCB DLBCL

Non-GCB DLBCL

Richter's Transformation

Transformed Lymphoid Malignancy

PCNSL or SCNSL of Breast or Testicular Origin

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.

Overall Response Rate

Duration of Response (DOR)

Progression Free Survival (PFS)

Treatment Emergent ADA

Neutralizing antibody Positive

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.

Number of Participants With Anti-Drug Antibodies (ADAs) to Tislelizumab

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.

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

Spots Global Cancer Trial Database for Zanubrutinib (BGB-3111) in Combination With Tislelizumab (BGB-A317) in Participants With B-cell Malignancies

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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Contact Details

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