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Trial record 1 of 1 for:    NCT04282018
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Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab

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ClinicalTrials.gov Identifier: NCT04282018
Recruitment Status : Recruiting
First Posted : February 24, 2020
Last Update Posted : January 26, 2024
Sponsor:
Information provided by (Responsible Party):
BeiGene

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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Follicular Lymphoma Marginal Zone Lymphoma Mantle Cell Lymphoma Diffuse Large B Cell Lymphoma Advanced Solid Tumor Drug: BGB-10188 Drug: Zanubrutinib Drug: Tislelizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 25, 2020
Estimated Primary Completion Date : February 13, 2025
Estimated Study Completion Date : February 13, 2025


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: BGB-10188
Administered as specified in the treatment arm

Drug: Zanubrutinib
Administered as specified in the treatment arm
Other Names:
  • BGB-3111
  • Brukinsa

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: BGB-10188
Administered as specified in the treatment arm

Drug: Zanubrutinib
Administered as specified in the treatment arm
Other Names:
  • BGB-3111
  • Brukinsa

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: BGB-10188
Administered as specified in the treatment arm

Drug: Tislelizumab
Administered as specified in the treatment arm
Other Name: BGB-A317

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: BGB-10188
Administered as specified in the treatment arm

Drug: Tislelizumab
Administered as specified in the treatment arm
Other Name: BGB-A317




Primary Outcome Measures :
  1. Part A: The recommended dose for expansion (RDFE) of BGB-10188 monotherapy [ Time Frame: Up to 8 Weeks ]
  2. Part B: RDFE of BGB-10188 in combination with zanubrutinib [ Time Frame: Up to 8 Weeks ]
  3. Part D: RDFE of BGB-10188 in combination with tislelizumab [ Time Frame: Up to 8 Weeks ]
  4. Part C and E: Overall response rate (ORR) [ Time Frame: Up to approximately 5 years and 6 months ]
    ORR is defined as the proportion of participants achieving a partial response (PR) or better

  5. 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 ]
  6. Parts A, B, D, and E: Number of participants experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to approximately 5 years and 6 months ]
  7. 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 Measures :
  1. Parts A, B, and D: Overall response rate (ORR) [ Time Frame: Up to approximately 5 years and 6 months ]
    ORR is defined as the proportion of participants achieving a partial response (PR) or better

  2. Parts B, C, D, and E: Duration of response (DOR) [ Time Frame: Up to approximately 5 years and 6 months ]
    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

  3. Parts B, C, D, and E: Time to response (TTR) [ Time Frame: Up to approximately 5 years and 6 months ]
    TTR is defined as the time from treatment initiation to the first documentation of response

  4. Parts C and E: Progression-free survival (PFS) [ Time Frame: Up to approximately 5 years and 6 months ]
    PFS is defined as the time from treatment initiation to the first documentation of progression or death due to any cause, whichever happens first

  5. Parts D and E: Disease control rate (DCR) [ Time Frame: Up to approximately 5 years and 6 months ]
  6. 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 ]
  7. 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 ]
  8. Part C: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 5 years and 6 months ]
  9. Part C: Number of participants experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to approximately 5 years and 6 months ]
  10. Part C: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation [ Time Frame: Up to approximately 5 years and 6 months ]
  11. Part E: Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 5 years and 6 months ]
    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

  12. Part E: CA-125 Response Rate [ Time Frame: Up to approximately 5 years and 6 months ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04282018


Contacts
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Contact: BeiGene 1-877-828-5568 clinicaltrials@beigene.com

Locations
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Australia, New South Wales
Blacktown Cancer and Haematology Centre Recruiting
Blacktown, New South Wales, Australia, 2148
Saint Vincents Hospital Sydney Recruiting
Darlinghurst, New South Wales, Australia, 2010
Australia, Queensland
Pindara Private Hospital Recruiting
Benowa, Queensland, Australia, 4217
Gallipoli Medical Research Foundation Recruiting
Greenslopes, Queensland, Australia, 4120
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Monash Health Recruiting
Clayton, Victoria, Australia, 3168
Australia, Western Australia
Perth Blood Institute Recruiting
West Perth, Western Australia, Australia, 6005
China, Jilin
The First Hospital of Jilin University Recruiting
Changchun, Jilin, China, 130021
China, Shandong
Jining No Peoples Hospital Recruiting
Jining, Shandong, China, 272000
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Study Director BeiGene
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT04282018    
Other Study ID Numbers: BGB-A317-3111-10188-101
First Posted: February 24, 2020    Key Record Dates
Last Update Posted: January 26, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes
Tislelizumab
Zanubrutinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action