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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia; Advanced Solid Tumor; Diffuse Large B Cell Lymphoma; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Tislelizumab; Drug: BGB-10188

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: 1-877-828-5568; Email: ClinicalTrials@beigene.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Recruiting
      • Blacktown Cancer and Haematology Centre
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • Saint Vincents Hospital Sydney
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Recruiting
      • Pindara Private Hospital
    • Greenslopes, Queensland, Australia, 4120
      • Recruiting
      • Gallipoli Medical Research Foundation
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health
  • Western Australia
    • West Perth, Western Australia, Australia, 6005
      • Recruiting
      • Perth Blood Institute
• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518036
      • Recruiting
      • Peking University Shenzhen Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The first hospital of Jilin University
  • Shandong
    • Jining, Shandong, China, 272000
      • Recruiting
      • Jining No Peoples Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: BGB-10188 Monotherapy Dose Escalation; BGB-10188 capsules administered orally once daily (QD) in 5 cohorts of escalating doses	Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: 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)	Drug: Zanubrutinib; Administered as specified in the treatment arm; Other Names: Brukinsa; BGB-3111; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: 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)	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: Part C: BGB-10188 + Zanubrutinib Dose Expansion; BGB-10188 capsules administered orally QD at RDFE of part B in combination with zanubrutinib 160mg (2*80mg capsules) administered orally BID	Drug: Zanubrutinib; Administered as specified in the treatment arm; Other Names: Brukinsa; BGB-3111; Drug: BGB-10188; Administered as specified in the treatment arm
Experimental: 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	Drug: Tislelizumab; Administered as specified in the treatment arm; Other Names: BGB-A317; Drug: BGB-10188; Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part C and 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
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
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

Outcome Measure	Measure Description	Time Frame
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
Parts B, C, 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
Parts B, C, 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
Parts C and 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
Parts D and E: Disease control rate (DCR)		Up to approximately 5 years and 6 months
Parts A, B, C, D, and E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188		Predose up to 7 days postdose
Parts A, B, C, D, and E: Area under the plasma concentration-time curve (AUC) of BGB-10188		Predose up to 7 days postdose
Part C: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)		Up to approximately 5 years and 6 months
Part C: Number of participants experiencing Severe Adverse Events (SAEs)		Up to approximately 5 years and 6 months
Part C: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation		Up to approximately 5 years and 6 months
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
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

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2020
• Primary Completion (Estimated): February 13, 2025
• Study Completion (Estimated): February 13, 2025

Study Registration Dates

• First Submitted: February 5, 2020
• First Submitted That Met QC Criteria: February 20, 2020
• First Posted (Actual): February 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; Hematologic Diseases; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Lymphoma, B-Cell; Chronic Disease; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Zanubrutinib; Tislelizumab
• Other Study ID Numbers: BGB-A317-3111-10188-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No