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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04282018
• Other study ID #: BGB-A317-3111-10188-101
• Secondary ID: CTR20220463
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 25, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: BeiGene
• Contact: BeiGene
• Phone: 1-877-828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 113
• Est. completion date: December 31, 2025
• Est. primary completion date: May 6, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• BGB-10188
Administered as specified in the treatment arm
• Zanubrutinib
Administered as specified in the treatment arm
• Tislelizumab
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Blacktown Cancer and Haematology Centre	Blacktown	New South Wales
Australia	Monash Health	Clayton	Victoria
Australia	Saint Vincents Hospital Sydney	Darlinghurst	New South Wales
Australia	Gallipoli Medical Research Foundation	Greenslopes	Queensland
China	Beijing Cancer Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Jining No Peoples Hospital	Jining	Shandong
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Union Hospital of Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: The recommended dose for expansion (RDFE) of BGB-10188 monotherapy		Up to 8 Weeks
Primary	Part B: RDFE of BGB-10188 in combination with zanubrutinib		Up to 8 Weeks
Primary	Part D: RDFE of BGB-10188 in combination with tislelizumab		Up to 8 Weeks
Primary	Part E: Overall response rate (ORR)	ORR is defined as the proportion of participants achieving a partial response (PR) or better	Up to approximately 5 years and 6 months
Primary	Parts A, B, D, and E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)		Up to approximately 5 years and 6 months
Primary	Parts A, B, D, and E: Number of participants experiencing Severe Adverse Events (SAEs)		Up to approximately 5 years and 6 months
Primary	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	Parts A, B, and D: Overall response rate (ORR)	ORR is defined as the proportion of participants achieving a partial response (PR) or better	Up to approximately 5 years and 6 months
Secondary	Parts B, D, and E: Duration of response (DOR)	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	Up to approximately 5 years and 6 months
Secondary	Parts B, D, and E: Time to response (TTR)	TTR is defined as the time from treatment initiation to the first documentation of response	Up to approximately 5 years and 6 months
Secondary	Part E: Progression-free survival (PFS)	PFS is defined as the time from treatment initiation to the first documentation of progression or death due to any cause, whichever happens first	Up to approximately 5 years and 6 months
Secondary	Parts D and E: Disease control rate (DCR)		Up to approximately 5 years and 6 months
Secondary	Parts A, B, D, and E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188		Predose up to 7 days postdose
Secondary	Parts A, B, D, and E: Area under the plasma concentration-time curve (AUC) of BGB-10188		Predose up to 7 days postdose
Secondary	Part E: Clinical Benefit Rate (CBR)	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	Up to approximately 5 years and 6 months
Secondary	Part E: CA-125 Response Rate	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	Up to approximately 5 years and 6 months