Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab

A Phase 1/2, Dose Escalation and Expansion Study of BGB-10188, a Phosphatidylinositol 3-Kinase Delta (PI3Kδ) Inhibitor, Combined With Zanubrutinib in Patients With Mature B-Cell Malignancies and Combined With Tislelizumab in Patients With Solid Tumors

The purpose of this study was to determine the maximum tolerated dose (MTD), recommended dose for expansion (RDFE), safety and tolerability of BGB-10188 as monotherapy in participants with relapsed/refractory (R/R) mature B-cell malignancies; in combination with zanubrutinib in participants with R/R follicular lymphoma (FL), R/R mantle cell lymphoma (MCL) or R/R diffuse large B-cell lymphoma (DLBCL); and in combination with tislelizumab in participants with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia; Advanced Solid Tumor; Diffuse Large B Cell Lymphoma; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Tislelizumab; Drug: BGB-10188

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Cancer and Haematology Centre
    • Darlinghurst, New South Wales, Australia, 2010
      • Saint Vincents Hospital Sydney
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Pindara Private Hospital
    • Greenslopes, Queensland, Australia, 4120
      • Gallipoli Medical Research Foundation
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
  • Western Australia
    • West Perth, Western Australia, Australia, 6005
      • Perth Blood Institute
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
  • Guangdong
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shandong
    • Jining, Shandong, China, 272000
      • Jining No Peoples Hospital West Branch
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Zhejiang University College of Medicine Second Affiliated Hospital
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Parts A, B and C

1. Confirmed diagnosis of one of the following:

   • Part A: R/R CLL/SLL, R/R MZL, R/R FL, R/R MCL or R/R DLBCL
   • Part B: R/R FL, R/R MCL, or R/R DLBCL
   • Part C: R/R FL, R/R MCL, or R/R DLBCL

   CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma; MZL = marginal zone lymphoma

2. Participants with MZL, FL, MCL, DLBCL, or SLL must have had at least one bi-dimensionally measurable nodal lesion greater than (>) 1.5 centimeters (cm) in the longest diameter or extranodal lesion that is > 1 cm in the longest diameter by computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by the Lugano Classification.

   Parts D and E

3. Part D: Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors previously treated with standard systemic therapy (including prior chemotherapy, radiotherapy, target therapy, and immunotherapy as locally, or guidance approved therapy) or for which treatment is not available or not tolerated. Enrollment was limited to participants with advanced solid tumors for which there was clinical evidence of response to T-cell based immuno-oncology agents (e.g., non-small cell lung cancer [NSCLC], small cell lung cancer [SCLC], head and neck squamous cell cancer, hepatocellular carcinoma, gastric or gastroesophageal junction carcinoma, nasopharyngeal carcinoma, renal cell carcinoma, cervical cancer, triple-negative breast cancer, ovarian cancer (OC), endometrial carcinoma, esophageal cancer, melanoma, urothelial carcinoma or participant with confirmed microsatellite instability-high [MSI-H] or mismatch repair deficient [dMMR] solid tumor, etc.). Enrollment of tumor types beyond above situations required sponsor's approval.
4. Part E: Participants with histologically or cytologically confirmed epithelial OC (including fallopian or primary peritoneal cancer) previously treated with 1 to 3 lines of systemic anticancer treatment; must have been platinum resistant and checkpoint inhibitor (CPI) naïve.
5. Participants must have had measurable disease as assessed by RECIST v1.1.

Key Exclusion Criteria:

Parts A, B and C

1. History of allogeneic stem-cell transplantation or chimeric antigen receptor-T (CAR-T) cell therapy.

2. For participants with DLBCL in Part A, classified as T-cell/histiocyte-rich large B-cell lymphoma, high-grade B-cell lymphoma with myelocytomatosis viral oncogene homolog and B-cell lymphoma (BCL)-2 and/or BCL-6 rearrangements, high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, Epstein-Barr virus positive DLBCL, and transformed DLBCL.

   Parts A, B, C, D and E

3. Prior exposure to PI3K inhibitor. For participants in Part B and Part C, prior exposure to BTK inhibitor and/or PI3K inhibitor.
4. Any approved anticancer therapy, including hormonal therapy, or any investigational agent or participation in another clinical study with therapeutic intent within 14 days before first dose.
5. Treatment with systemic immune-stimulatory agents (including, but not limited to, interferons and interleukin-2) within 2 weeks or 5 half-lives of the drug, whichever was later, before first dose.

6. Known human immunodeficiency virus (HIV) infection, or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows:

   • HBsAg (+), or
   • HBcAb (+) and HBV DNA detected, or
   • Presence of HCV antibody. Participants with presence of HCV antibody were eligible if HCV ribonucleic acid (RNA) was undetectable

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Dose Escalation- BGB-10188- 60 mg; Participants with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone lymphoma (MZL), follicular lymphoma (FL), mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL) received BGB-10188 60 milligrams (mg) orally, once daily (QD) from Cycle 1 day 1 (C1D1) until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.	Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part A: Dose Escalation- BGB-10188- 120 mg; Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 120 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.	Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part A: Dose Escalation- BGB-10188- 240 mg; Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 240 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.	Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part A: Dose Escalation- BGB-10188- 360 mg; Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 360 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.	Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part A: Dose Escalation- BGB-10188- 540 mg; Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 540 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.	Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part B: Dose Escalation- BGB-10188- 240 mg + Zanubrutinib-160 mg; Participants with R/R FL, MCL, and DLBCL received BGB-10188 240 mg orally, QD from C1D1 in combination with zanubrutinib 160 mg orally, twice a day (BID) until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.	Drug: Zanubrutinib; Administered as specified in the treatment arm; Other Names: Brukinsa; BGB-3111; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part D: Dose Escalation- BGB-10188- 20 mg + Tislelizumab 200 mg; Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 20 mg orally, QD from C1D1, followed by tislelizumab 200 mg intravenously (IV) on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Tevimbra; Tizveni; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part D: Dose Escalation- BGB-10188- 40 mg + Tislelizumab 200 mg; Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 40 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Tevimbra; Tizveni; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part D: Dose Escalation- BGB-10188- 80 mg + Tislelizumab 200 mg; Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 80 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Tevimbra; Tizveni; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part D: Dose Escalation- BGB-10188- 160 mg + Tislelizumab 200 mg; Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 160 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days, and the duration of each cycle from Cycle 2 onwards was 21 days.	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Tevimbra; Tizveni; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part D: Dose Escalation- BGB-10188- 320 mg + Tislelizumab 200 mg; Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 320 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Tevimbra; Tizveni; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part D: Dose Escalation- BGB-10188- 540 mg + Tislelizumab 200 mg; Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 540 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days, and the duration of each cycle from Cycle 2 onwards was 21 days.	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Tevimbra; Tizveni; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part E: Dose Expansion- BGB-10188- 160 mg + Tislelizumab 200 mg; Participants with platinum-resistant ovarian cancer (PROC) were randomized to receive BGB-10188 160 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on Day 1 of each cycle until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 21 days.	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Tevimbra; Tizveni; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part E: Dose Expansion- BGB-10188- 320 mg + Tislelizumab 200 mg; Participants with PROC were randomized to receive BGB-10188 320 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on Day 1 of each cycle until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 21 days.	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Tevimbra; Tizveni; Drug: BGB-10188; Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: The Recommended Dose for Expansion (RDFE) of BGB-10188 Monotherapy in Hematologic Malignancies	The RDFE of BGB-10188 monotherapy in participants with hematologic malignancies was planned to be determined from safety, tolerability, pharmacokinetic (PK), and any other relevant and available data based on recommendations from the Safety Monitoring Committee. Part A dose-escalation enrolled participants with R/R CLL/SLL, MZL, FL, MCL, and DLBCL up to 540 mg, however the maximum tolerated dose was not reached and the RDFE could not be determined based on the data that were collected.	Up to 28 days
Part B: The RDFE of BGB-10188 in Combination With Zanubrutinib in Hematologic Malignancies	The RDFE of BGB-10188 in combination with zanubrutinib was planned to be determined from safety, tolerability, PK, and any other relevant and available data obtained, based on recommendation of the Safety Monitoring Committee. The RDFE could not be determined since not all planned dose cohorts in this part of the study were enrolled and not enough data were collected to establish the RDFE.	Up to 28 days
Part D: The RDFE of BGB-10188 in Combination With Tislelizumab in Advanced Solid Tumors	The RDFE of BGB-10188 in combination with tislelizumab was determined based on the totality of safety, tolerability, PK, and any other relevant and available data that were obtained from the dose escalation phase for Part E.	Up to 28 days
Part E: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1	ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR). Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to 10.0 months
Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation	An AE was defined as any unfavorable and unintended sign, symptom, or disease associated with the use of study drugs, whether considered related to study drugs or not. An SAE was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly or was considered a medically significant. TEAE was an AE that has an onset date or a worsening in severity from baseline on or after the first dose of study drug. Severity of AEs was assessed according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v.5.0, which consists of: Grade 1 Mild; Grade 2 Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death due to AE.	Part A: 47.2 Months; Part B: 24 Months; Part D: 15.2 Months; Part E: 10 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A and B: ORR as Assessed by Investigator	ORR was defined as the percentage of participants who had CR or PR as determined from investigator-derived tumor assessments per RECIST v. 1.1. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Part A: up to 47.2 months and Part B: up to 24 months
Part A: Observed Maximum Plasma Concentration (Cmax) of BGB-10188 After a Single Dose	Cmax of BGB-10188 after a single dose was determined.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 168 hours post-dose on Day -7 (each cycle = 28 days)
Part A: Cmax of BGB-10188 at Steady State	Cmax of BGB-10188 at steady state was determined.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 15 (each cycle = 28 days)
Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) After Single Dose	Area under the plasma concentration-time curve of BGB-10188 from time 0 to 24 hours (AUC0-24) was determined.	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8,12, and 24 hours post-dose on Day-7 (each cycle = 28 days)
Part B: Duration of Response (DOR)	DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of progression (PD) or death, whichever came first. Median DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	Up to 24 months
Part B: Time to Response (TTR)	TRR was defined as the time from treatment initiation to the first documentation of response. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to 24 months
Part B: Cmax of BGB-10188 After a Single Dose	Cmax of BGB-10188 after a single dose when given in combination with zanubrutinib was determined.	Pre-dose, 0.5,1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)
Part B: Cmax of BGB-10188 at Steady State	Cmax of BGB-10188 at steady state when given in combination with zanubrutinib was determined.	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 15 (each cycle = 28 days)
Part B: AUC 0-24 h of BGB-10188 After a Single Dose	AUC 0-24 h of BGB-10188 after a single dose when given in combination with zanubrutinib was determined.	Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)
Part D: Overall Response Rate (ORR)	ORR was defined as the percentage of participants who had CR or PR as determined from investigator-derived tumor assessments per RECIST v. 1.1. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Up to 15.2 months
Parts D and E: Duration of Response (DOR)	DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of PD or death, whichever came first. Median DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment.	Part D: up to 15.2 months and Part E: up to 10.0 months
Parts D and E: Disease Control Rate (DCR)	DCR was defined as the percentage of participants with best overall response (BOR), as per RECIST v.1.1, of a CR, PR, or stable disease (SD). Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Part D: up to 15.2 months and Part E: up to 10.0 months
Parts D and E: Time to Response (TTR)	TTR was defined as the time from treatment initiation to the first documentation of response. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	Part D: up to 15.2 months and Part E: up to 10.0 months
Part D: Cmax of BGB-10188 After a Single Dose	Cmax of BGB-10188 after a single dose when given in combination with tislelizumab was determined.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)
Part D: Cmax of BGB-10188 at Steady State	Cmax of BGB-10188 at steady state when given in combination with tislelizumab was determined.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)
Part D: AUC 0-24h of BGB-10188 After Single Dose	AUC 0-24 h of BGB-10188 after a single dose when given in combination with tislelizumab was determined.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)
Part D: AUC 0-24h of BGB-10188 at Steady State	AUC 0-24 h of BGB-10188 at steady state when given in combination with tislelizumab was determined.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)
Part E: Progression-Free Survival (PFS)	PFS was defined as the time from the date of the first dose of study drugs to the date of the first documentation of PD assessed by the investigator using RECIST v1.1 or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.	Up to 10.0 months
Part E: Clinical Benefit Rate (CBR)	CBR was defined as the percentage of participants with best overall response, as defined by RECIST v1.1, of a CR, PR, or at least 24 weeks of SD. Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions, and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Up to 10.0 months
Part E: Cancer Antigen (CA)-125 Response Rate Per Gynecological Cancer Intergroup	CA-125 response rate was defined as the percentage of participants achieving a CA-125 response according to the Gynecological Cancer Center Intergroup criteria, in which a response had occurred if there was at least a 50% reduction in CA-125 levels from baseline.	Up to 10.0 months
Part E: Cmax of BGB-10188 After Single Dose	Cmax of BGB-10188 after a single dose when given in combination with tislelizumab was determined.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 1 (each cycle = 21 days)
Part E: Cmax of BGB-10188 at Steady State	Cmax of BGB-10188 at steady state when given in combination with tislelizumab was determined.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)
Part E: AUC0-24h of BGB-10188 After Single Dose	AUC0-24 h of BGB-10188 after a single dose when given in combination with tislelizumab was determined.	Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose of Cycle 1 Day 1 (each cycle = 21 days)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2020
• Primary Completion (Actual): August 28, 2024
• Study Completion (Actual): August 28, 2024

Study Registration Dates

• First Submitted: February 5, 2020
• First Submitted That Met QC Criteria: February 20, 2020
• First Posted (Actual): February 24, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib; tislelizumab
• Other Study ID Numbers: BGB-A317-3111-10188-101; CTR20220463 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No