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

NCT ID: NCT04282018

Last Updated: 2024-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

97 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-25

Study Completion Date

2024-08-28

Brief Summary

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The purpose of this study is 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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A: BGB-10188 Monotherapy Dose Escalation

BGB-10188 capsules administered orally once daily (QD) in 5 cohorts of escalating doses

Group Type EXPERIMENTAL

BGB-10188

Intervention Type DRUG

Administered as specified in the treatment arm

Part B: BGB-10188 + Zanubrutinib Dose Escalation

BGB-10188 capsules administered orally QD at the latest cleared dose of BGB-10188 monotherapy (Part A) in combination with zanubrutinib 160mg (2\*80mg capsules) administered orally twice daily (BID)

Group Type EXPERIMENTAL

BGB-10188

Intervention Type DRUG

Administered as specified in the treatment arm

Zanubrutinib

Intervention Type DRUG

Administered as specified in the treatment arm

Part C: BGB-10188 + Zanubrutinib Dose Expansion

This Part was originally planned but was cancelled by the sponsor and will not be initiated.

Group Type EXPERIMENTAL

BGB-10188

Intervention Type DRUG

Administered as specified in the treatment arm

Zanubrutinib

Intervention Type DRUG

Administered as specified in the treatment arm

Part D: BGB-10188 + Tislelizumab Infusion Dose Escalation

BGB-10188 capsules administered orally QD in up to 6 cohorts of escalating doses in combination with tislelizumab 200mg IV infusion administered every 3 weeks (Q3W)

Group Type EXPERIMENTAL

BGB-10188

Intervention Type DRUG

Administered as specified in the treatment arm

Tislelizumab

Intervention Type DRUG

Administered as specified in the treatment arm

Part E: BGB-10188 + Tislelizumab Infusion Dose Expansion

BGB-10188 capsules administered orally QD at two doses in combination with tislelizumab 200mg IV infusion administered Q3W

Group Type EXPERIMENTAL

BGB-10188

Intervention Type DRUG

Administered as specified in the treatment arm

Tislelizumab

Intervention Type DRUG

Administered as specified in the treatment arm

Interventions

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BGB-10188

Administered as specified in the treatment arm

Intervention Type DRUG

Zanubrutinib

Administered as specified in the treatment arm

Intervention Type DRUG

Tislelizumab

Administered as specified in the treatment arm

Intervention Type DRUG

Other Intervention Names

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BGB-3111 Brukinsa BGB-A317 Tevimbra Tizveni

Eligibility Criteria

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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 at least one bi-dimensionally measurable nodal lesion \>1.5 cm in the longest diameter or extranodal lesion that is \> 1cm 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 will be limited to participants with advanced solid tumors for which there is clinical evidence of response to T-cell based immuno-oncology agents (eg, 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 requires 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 be platinum resistant and checkpoint inhibitor (CPI) naïve.
5. Participants must have measurable disease as assessed by RECIST v1.1.

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 is 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 are eligible if HCV ribonucleic acid (RNA) is undetectable
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeiGene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

BeiGene

Locations

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Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, Australia

Site Status

Saint Vincents Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

Pindara Private Hospital

Benowa, Queensland, Australia

Site Status

Gallipoli Medical Research Foundation

Greenslopes, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Monash Health

Clayton, Victoria, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Perth Blood Institute

West Perth, Western Australia, Australia

Site Status

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

Site Status

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status

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

Wuhan, Hubei, China

Site Status

Hubei Cancer Hospital

Wuhan, Hubei, China

Site Status

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status

The First Hospital of Jilin University

Changchun, Jilin, China

Site Status

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, China

Site Status

Jining No Peoples Hospital West Branch

Jining, Shandong, China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Site Status

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status

Zhejiang University College of Medicine Second Affiliated Hospital

Hangzhou, Zhejiang, China

Site Status

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status

Countries

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Australia China

Other Identifiers

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CTR20220463

Identifier Type: OTHER

Identifier Source: secondary_id

BGB-A317-3111-10188-101

Identifier Type: -

Identifier Source: org_study_id