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

Primary Purpose

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Follicular Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BGB-10188
Zanubrutinib
Tislelizumab
Sponsored by
BeiGene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, 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.
  4. 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.
  5. Participants must have ≥1 measurable lesion as defined by RECIST v1.1.

Key Exclusion Criteria:

Parts A, B and C

  1. History of allogeneic stem-cell transplantation or 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 (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

  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.

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

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

Arm Description

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

Outcomes

Primary Outcome Measures

Part A: The recommended dose for expansion (RDFE) of BGB-10188 monotherapy
Part B: RDFE of BGB-10188 in combination with zanubrutinib
Part D: RDFE of BGB-10188 in combination with tislelizumab
Part C and E: Overall response rate (ORR)
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)
Parts A, B, D, and E: Number of participants experiencing Severe Adverse Events (SAEs)
Parts A, B, D and E: Number of participants experiencing Adverse Events (AEs) Leading to Discontinuation

Secondary Outcome Measures

Parts A, B, and D: Overall response rate (ORR)
ORR is defined as the proportion of participants achieving a partial response (PR) or better
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
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
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
Parts D and E: Disease control rate (DCR)
Parts A, B, C, D, and E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188
Parts A, B, C, D, and E: Area under the plasma concentration-time curve (AUC) of BGB-10188
Part C: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
Part C: Number of participants experiencing Severe Adverse Events (SAEs)
Part C: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation
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
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

Full Information

First Posted
February 5, 2020
Last Updated
September 26, 2023
Sponsor
BeiGene
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1. Study Identification

Unique Protocol Identification Number
NCT04282018
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2020 (Actual)
Primary Completion Date
February 13, 2025 (Anticipated)
Study Completion Date
February 13, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Diffuse Large B Cell Lymphoma, Advanced Solid Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
126 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part A: BGB-10188 Monotherapy Dose Escalation
Arm Type
Experimental
Arm Description
BGB-10188 capsules administered orally once daily (QD) in 5 cohorts of escalating doses
Arm Title
Part B: BGB-10188 + Zanubrutinib Dose Escalation
Arm Type
Experimental
Arm Description
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)
Arm Title
Part C: BGB-10188 + Zanubrutinib Dose Expansion
Arm Type
Experimental
Arm Description
BGB-10188 capsules administered orally QD at RDFE of part B in combination with zanubrutinib 160mg (2*80mg capsules) administered orally BID
Arm Title
Part D: BGB-10188 + Tislelizumab Infusion Dose Escalation
Arm Type
Experimental
Arm Description
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)
Arm Title
Part E: BGB-10188 + Tislelizumab Infusion Dose Expansion
Arm Type
Experimental
Arm Description
BGB-10188 capsules administered orally QD at two doses in combination with tislelizumab 200mg IV infusion administered Q3W
Intervention Type
Drug
Intervention Name(s)
BGB-10188
Intervention Description
Administered as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Other Intervention Name(s)
BGB-3111, Brukinsa
Intervention Description
Administered as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Other Intervention Name(s)
BGB-A317
Intervention Description
Administered as specified in the treatment arm
Primary Outcome Measure Information:
Title
Part A: The recommended dose for expansion (RDFE) of BGB-10188 monotherapy
Time Frame
Up to 8 Weeks
Title
Part B: RDFE of BGB-10188 in combination with zanubrutinib
Time Frame
Up to 8 Weeks
Title
Part D: RDFE of BGB-10188 in combination with tislelizumab
Time Frame
Up to 8 Weeks
Title
Part C and E: Overall response rate (ORR)
Description
ORR is defined as the proportion of participants achieving a partial response (PR) or better
Time Frame
Up to approximately 5 years and 6 months
Title
Parts A, B, D, and E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
Time Frame
Up to approximately 5 years and 6 months
Title
Parts A, B, D, and E: Number of participants experiencing Severe Adverse Events (SAEs)
Time Frame
Up to approximately 5 years and 6 months
Title
Parts A, B, D and E: Number of participants experiencing Adverse Events (AEs) Leading to Discontinuation
Time Frame
Up to approximately 5 years and 6 months
Secondary Outcome Measure Information:
Title
Parts A, B, and D: Overall response rate (ORR)
Description
ORR is defined as the proportion of participants achieving a partial response (PR) or better
Time Frame
Up to approximately 5 years and 6 months
Title
Parts B, C, D, and E: Duration of response (DOR)
Description
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
Time Frame
Up to approximately 5 years and 6 months
Title
Parts B, C, D, and E: Time to response (TTR)
Description
TTR is defined as the time from treatment initiation to the first documentation of response
Time Frame
Up to approximately 5 years and 6 months
Title
Parts C and E: Progression-free survival (PFS)
Description
PFS is defined as the time from treatment initiation to the first documentation of progression or death due to any cause, whichever happens first
Time Frame
Up to approximately 5 years and 6 months
Title
Parts D and E: Disease control rate (DCR)
Time Frame
Up to approximately 5 years and 6 months
Title
Parts A, B, C, D, and E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188
Time Frame
Predose up to 7 days postdose
Title
Parts A, B, C, D, and E: Area under the plasma concentration-time curve (AUC) of BGB-10188
Time Frame
Predose up to 7 days postdose
Title
Part C: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
Time Frame
Up to approximately 5 years and 6 months
Title
Part C: Number of participants experiencing Severe Adverse Events (SAEs)
Time Frame
Up to approximately 5 years and 6 months
Title
Part C: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation
Time Frame
Up to approximately 5 years and 6 months
Title
Part E: Clinical Benefit Rate (CBR)
Description
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
Time Frame
Up to approximately 5 years and 6 months
Title
Part E: CA-125 Response Rate
Description
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
Time Frame
Up to approximately 5 years and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, 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. 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. Participants must have measurable disease as assessed by RECIST v1.1. Key Exclusion Criteria: Parts A, B and C History of allogeneic stem-cell transplantation or chimeric antigen receptor-T (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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
BeiGene
Phone
1-877-828-5568
Email
clinicaltrials@beigene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
BeiGene
Official's Role
Study Director
Facility Information:
Facility Name
Blacktown Cancer and Haematology Centre
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Individual Site Status
Recruiting
Facility Name
Saint Vincents Hospital Sydney
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Individual Site Status
Recruiting
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Monash Health
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Name
Perth Blood Institute
City
West Perth
State/Province
Western Australia
ZIP/Postal Code
6005
Country
Australia
Individual Site Status
Recruiting
Facility Name
Fujian Cancer Hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350014
Country
China
Individual Site Status
Recruiting
Facility Name
The Third Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Name
Jining No Peoples Hospital
City
Jining
State/Province
Shandong
ZIP/Postal Code
272000
Country
China
Individual Site Status
Recruiting
Facility Name
Affiliated Zhongshan Hospital of Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Name
West China Hospital, Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Name
Zhejiang University College of Medicine Second Affiliated Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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