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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 9, 2023
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
The purpose of this study is to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), 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 Non-small Cell Lung Cancer Small Cell Lung Cancer Metastatic Melanoma Drug: BGB-10188 Drug: Zanubrutinib Drug: Tislelizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 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 : March 26, 2025
Estimated Study Completion Date : November 7, 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 RP2D 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 RP2D of part D 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 Phase 2 dose (RP2D) of BGB-10188 monotherapy [ Time Frame: Up to 8 Weeks ]
  2. Part B: RP2D of BGB-10188 in combination with zanubrutinib [ Time Frame: Up to 8 Weeks ]
  3. Part D: RP2D 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, and D: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 5 years and 6 months ]
  6. Parts A, B, and D: Number of participants experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to approximately 5 years and 6 months ]
  7. Parts A, B and D: 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. Parts C and E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to approximately 5 years and 6 months ]
  9. Parts C and E: Number of participants experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to approximately 5 years and 6 months ]
  10. Parts C and E: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation [ Time Frame: Up to approximately 5 years and 6 months ]


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, 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.


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
Hematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital Recruiting
Adelaide, Australia, 5000
Blacktown Hospital Recruiting
Blacktown, Australia, 2148
Monash Hospital - Hematology Recruiting
Clayton, Australia
St. Vincent Hospital - Sydney - Hematology/Oncology Recruiting
Darlinghurst, Australia
Austin Hospital - Hematology Recruiting
Heidelberg, Australia
Perth Blood Institute Recruiting
West Perth, Australia
China, Fujian
Fujian Cancer Hospital Recruiting
Fuzhou, Fujian, China, 350014
China, Hangzhou
Second Affiliated Hospital of Zhejiang University School of Medicine Recruiting
Zhejiang, Hangzhou, China, 310009
China, Hunan
Third Xiangya Hospital of Central South University Recruiting
Changsha, Hunan, China
China, Jiangsu
First Affiliated Hospital of Soochow University Recruiting
Suzhou, Jiangsu, China
China, Shandong
Jining No. 1 People's Hospital Recruiting
Jining, Shandong, China, 272073
China, Shanghai
Fudan University Zhongshan Hospital Recruiting
Shanghai, Shanghai, China, 200032
China, Sichuan
West China Hospital Recruiting
Chengdu, Sichuan, China, 610041
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 9, 2023
Last Verified: January 2023
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
Lung Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Small Cell Lung Carcinoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia
Lymphoma, B-Cell
Leukemia, B-Cell
Zanubrutinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action