Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Follicular Lymphoma
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia
Eligibility Criteria
Key Inclusion Criteria:
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
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
- 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, anti PD-1, 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, 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.
- Part E: Participants with NSCLC or metastatic melanoma that has progressed from PD 1/PD-L1 antibody treatment or participants with SCLC with no prior PD 1/PD-L1 antibody treatment.
- Participants must have ≥1 measurable lesion as defined by RECIST v1.1.
Key Exclusion Criteria:
Parts A, B and C
- History of allogeneic stem-cell transplantation or 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 (MYC) 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 is 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 are eligible if HCV ribonucleic acid (RNA) is undetectable
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Blacktown Cancer and Haematology CentreRecruiting
- Saint Vincents Hospital SydneyRecruiting
- Royal Adelaide HospitalRecruiting
- Monash HealthRecruiting
- Austin HealthRecruiting
- Perth Blood InstituteRecruiting
- Fujian Cancer HospitalRecruiting
- The Third Xiangya Hospital of Central South UniversityRecruiting
- The First Affiliated Hospital of Soochow UniversityRecruiting
- Jining No Peoples HospitalRecruiting
- Affiliated Zhongshan Hospital of Fudan UniversityRecruiting
- West China Hospital, Sichuan UniversityRecruiting
- Zhejiang University College of Medicine Second Affiliated HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Part A: BGB-10188 Monotherapy Dose Escalation
Part B: BGB-10188 + Zanubrutinib Dose Escalation
Part C: BGB-10188 + Zanubrutinib Dose Expansion
Part D: BGB-10188 + Tislelizumab Infusion Dose Escalation
Part E: BGB-10188 + Tislelizumab Infusion Dose Expansion
BGB-10188 capsules administered orally once daily (QD) in 5 cohorts of escalating doses
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)
BGB-10188 capsules administered orally QD at RDFE of part B in combination with zanubrutinib 160mg (2*80mg capsules) administered orally BID
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)
BGB-10188 capsules administered orally QD at two doses in combination with tislelizumab 200mg IV infusion administered Q3W