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

NCT04282018 | Completed Phase 1 Results

• 2 other identifiers: BGB-A317-3111-10188-101CTR20220463
• Study Type: interventional
• Target: 97
• Locations: 2 countries
• Sites: 24

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma; Mantle Cell Lymphoma; Diffuse Large B Cell Lymphoma; Advanced Solid Tumor

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (23)

• Parts A and B: ORR as Assessed by Investigator

  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

  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

  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

  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)

  Up to 24 months

Study Arms (14)

Part A: Dose Escalation- BGB-10188- 60 mg

EXPERIMENTAL

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

Part A: Dose Escalation- BGB-10188- 120 mg

EXPERIMENTAL

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

Part A: Dose Escalation- BGB-10188- 240 mg

EXPERIMENTAL

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

Part A: Dose Escalation- BGB-10188- 360 mg

EXPERIMENTAL

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

Part A: Dose Escalation- BGB-10188- 540 mg

EXPERIMENTAL

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

Part B: Dose Escalation- BGB-10188- 240 mg + Zanubrutinib-160 mg

EXPERIMENTAL

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: BGB-10188; Drug: Zanubrutinib

Part D: Dose Escalation- BGB-10188- 20 mg + Tislelizumab 200 mg

EXPERIMENTAL

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: BGB-10188; Drug: Tislelizumab

Part D: Dose Escalation- BGB-10188- 40 mg + Tislelizumab 200 mg

EXPERIMENTAL

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: BGB-10188; Drug: Tislelizumab

Part D: Dose Escalation- BGB-10188- 80 mg + Tislelizumab 200 mg

EXPERIMENTAL

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: BGB-10188; Drug: Tislelizumab

Part D: Dose Escalation- BGB-10188- 160 mg + Tislelizumab 200 mg

EXPERIMENTAL

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: BGB-10188; Drug: Tislelizumab

Part D: Dose Escalation- BGB-10188- 320 mg + Tislelizumab 200 mg

EXPERIMENTAL

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: BGB-10188; Drug: Tislelizumab

Part D: Dose Escalation- BGB-10188- 540 mg + Tislelizumab 200 mg

EXPERIMENTAL

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: BGB-10188; Drug: Tislelizumab

Part E: Dose Expansion- BGB-10188- 160 mg + Tislelizumab 200 mg

EXPERIMENTAL

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: BGB-10188; Drug: Tislelizumab

Part E: Dose Expansion- BGB-10188- 320 mg + Tislelizumab 200 mg

EXPERIMENTAL

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: BGB-10188; Drug: Tislelizumab

Interventions

BGB-10188 DRUG

Administered as specified in the treatment arm

Part A: Dose Escalation- BGB-10188- 120 mg; Part A: Dose Escalation- BGB-10188- 240 mg; Part A: Dose Escalation- BGB-10188- 360 mg; Part A: Dose Escalation- BGB-10188- 540 mg; Part A: Dose Escalation- BGB-10188- 60 mg; Part B: Dose Escalation- BGB-10188- 240 mg + Zanubrutinib-160 mg; Part D: Dose Escalation- BGB-10188- 160 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 20 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 320 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 40 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 540 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 80 mg + Tislelizumab 200 mg; Part E: Dose Expansion- BGB-10188- 160 mg + Tislelizumab 200 mg; Part E: Dose Expansion- BGB-10188- 320 mg + Tislelizumab 200 mg

Zanubrutinib DRUG

Administered as specified in the treatment arm

Also known as: BGB-3111, Brukinsa

Part B: Dose Escalation- BGB-10188- 240 mg + Zanubrutinib-160 mg

Tislelizumab DRUG

Administered as specified in the treatment arm

Also known as: BGB-A317, Tevimbra, Tizveni

Part D: Dose Escalation- BGB-10188- 160 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 20 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 320 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 40 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 540 mg + Tislelizumab 200 mg; Part D: Dose Escalation- BGB-10188- 80 mg + Tislelizumab 200 mg; Part E: Dose Expansion- BGB-10188- 160 mg + Tislelizumab 200 mg; Part E: Dose Expansion- BGB-10188- 320 mg + Tislelizumab 200 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parts A, B and C
• 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
• 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
• 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.
• 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.
• Participants must have had measurable disease as assessed by RECIST v1.1.

You may not qualify if:

• Parts A, B and C
• History of allogeneic stem-cell transplantation or chimeric antigen receptor-T (CAR-T) cell therapy.
• 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
• Prior exposure to PI3K inhibitor. For participants in Part B and Part C, prior exposure to BTK inhibitor and/or PI3K inhibitor.
• 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.
• 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.
• 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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (24)

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, 2148, Australia

Location

Saint Vincents Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

Location

Gallipoli Medical Research Foundation

Greenslopes, Queensland, 4120, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Perth Blood Institute

West Perth, Western Australia, 6005, Australia

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

Location

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, 750004, China

Location

Jining No Peoples Hospital West Branch

Jining, Shandong, 272000, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Zhejiang University College of Medicine Second Affiliated Hospital

Hangzhou, Zhejiang, 310009, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse

Interventions

zanubrutinib; tislelizumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell

Limitations and Caveats

Part C was cancelled by the sponsor and not initiated.

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 24, 2020
• Study Start: April 29, 2020
• Primary Completion: August 28, 2024
• Study Completion: August 28, 2024
• Last Updated: February 20, 2026
• Results First Posted: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

AU (8); CN (16)