Clinical trial NCT04282018: Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Follicular Lymphoma
Marginal Zone Lymphoma
Mantle Cell Lymphoma
Diffuse Large B Cell Lymphoma
Advanced Solid Tumor
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2020-02-24
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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.

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 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

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

Primary outcomes:
measure: Part A: The recommended dose for expansion (RDFE) of BGB-10188 monotherapy
timeFrame: Up to 8 Weeks
measure: Part B: RDFE of BGB-10188 in combination with zanubrutinib
timeFrame: Up to 8 Weeks
measure: Part D: RDFE of BGB-10188 in combination with tislelizumab
timeFrame: Up to 8 Weeks
measure: Part E: Overall response rate (ORR)
timeFrame: Up to approximately 5 years and 6 months
measure: Parts A, B, D, and E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 5 years and 6 months
measure: Parts A, B, D, and E: Number of participants experiencing Severe Adverse Events (SAEs)
timeFrame: Up to approximately 5 years and 6 months
measure: Parts A, B, D and E: Number of participants experiencing Adverse Events (AEs) Leading to Discontinuation
timeFrame: Up to approximately 5 years and 6 months
Secondary outcomes:
measure: Parts A, B, and D: Overall response rate (ORR)
timeFrame: Up to approximately 5 years and 6 months
measure: Parts B, D, and E: Duration of response (DOR)
timeFrame: Up to approximately 5 years and 6 months
measure: Parts B, D, and E: Time to response (TTR)
timeFrame: Up to approximately 5 years and 6 months
measure: Part E: Progression-free survival (PFS)
timeFrame: Up to approximately 5 years and 6 months
measure: Parts D and E: Disease control rate (DCR)
timeFrame: Up to approximately 5 years and 6 months
measure: Parts A, B, D, and E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188
timeFrame: Predose up to 7 days postdose
measure: Parts A, B, D, and E: Area under the plasma concentration-time curve (AUC) of BGB-10188
timeFrame: Predose up to 7 days postdose
measure: Part E: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 5 years and 6 months
measure: Part E: CA-125 Response Rate
timeFrame: Up to approximately 5 years and 6 months
Other outcomes:
Locations:
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Darlinghurst
country: Australia
facility: Saint Vincents Hospital Sydney
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Foundation
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: West Perth
country: Australia
facility: Perth Blood Institute
state: Western Australia
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jining
country: China
facility: Jining No Peoples Hospital West Branch
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang University College of Medicine Second Affiliated Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: