Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab
- Conditions
- Chronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaFollicular LymphomaMarginal Zone LymphomaMantle Cell LymphomaDiffuse Large B Cell LymphomaAdvanced Solid Tumor
- Interventions
- Registration Number
- NCT04282018
- Lead Sponsor
- BeiGene
- Brief Summary
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
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
Parts A, B and C
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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
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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
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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.
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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.
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Participants must have measurable disease as assessed by RECIST v1.1.
Key
Parts A, B and C
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History of allogeneic stem-cell transplantation or chimeric antigen receptor-T (CAR-T) cell therapy.
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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
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Prior exposure to PI3K inhibitor. For participants in Part B and Part C, prior exposure to BTK inhibitor and/or PI3K inhibitor.
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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.
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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.
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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
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: BGB-10188 + Zanubrutinib Dose Escalation BGB-10188 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) Part D: BGB-10188 + Tislelizumab Infusion Dose Escalation BGB-10188 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) Part E: BGB-10188 + Tislelizumab Infusion Dose Expansion Tislelizumab BGB-10188 capsules administered orally QD at two doses in combination with tislelizumab 200mg IV infusion administered Q3W Part C: BGB-10188 + Zanubrutinib Dose Expansion Zanubrutinib This Part was originally planned but was cancelled by the sponsor and will not be initiated. Part D: BGB-10188 + Tislelizumab Infusion Dose Escalation Tislelizumab 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) Part E: BGB-10188 + Tislelizumab Infusion Dose Expansion BGB-10188 BGB-10188 capsules administered orally QD at two doses in combination with tislelizumab 200mg IV infusion administered Q3W Part A: BGB-10188 Monotherapy Dose Escalation BGB-10188 BGB-10188 capsules administered orally once daily (QD) in 5 cohorts of escalating doses Part B: BGB-10188 + Zanubrutinib Dose Escalation Zanubrutinib 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) Part C: BGB-10188 + Zanubrutinib Dose Expansion BGB-10188 This Part was originally planned but was cancelled by the sponsor and will not be initiated.
- Primary Outcome Measures
Name Time Method Part A: The recommended dose for expansion (RDFE) of BGB-10188 monotherapy Up to 8 Weeks Part B: RDFE of BGB-10188 in combination with zanubrutinib Up to 8 Weeks Part D: RDFE of BGB-10188 in combination with tislelizumab Up to 8 Weeks Part E: Overall response rate (ORR) Up to approximately 5 years and 6 months ORR is defined as the proportion of participants achieving a partial response (PR) or better
Parts A, B, D, and E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) Up to approximately 5 years and 6 months Parts A, B, D, and E: Number of participants experiencing Severe Adverse Events (SAEs) Up to approximately 5 years and 6 months Parts A, B, D and E: Number of participants experiencing Adverse Events (AEs) Leading to Discontinuation Up to approximately 5 years and 6 months
- Secondary Outcome Measures
Name Time Method Part E: CA-125 Response Rate Up to approximately 5 years and 6 months CA-125 response rate is defined as the proportion of participants achieving a CA-125 response according to the Gynecological Cancer Center Intergroup criteria; a response has occurred if there is at least a 50% reduction in CA-125 levels from baseline
Parts A, B, and D: Overall response rate (ORR) Up to approximately 5 years and 6 months ORR is defined as the proportion of participants achieving a partial response (PR) or better
Parts B, D, and E: Duration of response (DOR) Up to approximately 5 years and 6 months DOR is defined as the time from the first response documentation to the date that progression is documented after treatment initiation or death, whichever occurs first
Parts B, D, and E: Time to response (TTR) Up to approximately 5 years and 6 months TTR is defined as the time from treatment initiation to the first documentation of response
Part E: Progression-free survival (PFS) Up to approximately 5 years and 6 months PFS is defined as the time from treatment initiation to the first documentation of progression or death due to any cause, whichever happens first
Parts D and E: Disease control rate (DCR) Up to approximately 5 years and 6 months Parts A, B, D, and E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188 Predose up to 7 days postdose Parts A, B, D, and E: Area under the plasma concentration-time curve (AUC) of BGB-10188 Predose up to 7 days postdose Part E: Clinical Benefit Rate (CBR) Up to approximately 5 years and 6 months CBR is defined as proportion of participants with best overall response, as defined by RECIST v1.1, of a CR, PR, or at least 24 weeks of stable disease
Trial Locations
- Locations (14)
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Saint Vincents Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Pindara Private Hospital
🇦🇺Benowa, Queensland, Australia
Gallipoli Medical Research Foundation
🇦🇺Greenslopes, Queensland, Australia
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Jining No Peoples Hospital
🇨🇳Jining, Shandong, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Monash Health
🇦🇺Clayton, Victoria, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Perth Blood Institute
🇦🇺West Perth, Western Australia, Australia