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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04282018
Recruitment Status : Recruiting
First Posted : February 24, 2020
Last Update Posted : September 29, 2020
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 & tolerability of BGB-10188: as monotherapy in participants with mature B-cell malignancies; oin combination with zanubrutinib in participants with relapse/refractory follicular lymphoma (R/R FL), mantle cell lymphoma (MCL) or 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 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 : April 26, 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 a dose level less than RP2D and RP2D 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

Experimental: Part C: BGB-10188 + Zanubrutinib Dose Expansion
BGB-10188 capsules administered orally QD at RP2D of part B in combination with zanbrutinib 160mg (2*80mg capsules) administered orally BID
Drug: BGB-10188
Administered as specified in the treatment arm

Drug: Tislelizumab
Administered as specified in the treatment arm

Experimental: Part D: BGB-10188 + Tislelizumab Infusion Dose Escalation
BGB-10188 capsules administered orally QD in upto 4 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: Zanubrutinib
Administered as specified in the treatment arm

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




Primary Outcome Measures :
  1. Part A: The maximum tolerated dose (MTD) of BGB-10188 monotherapy [ Time Frame: Up to 8 Weeks ]
  2. Part A: The recommended Phase 2 dose (RP2D) of BGB-10188 monotherapy in mature B-cell malignancies [ Time Frame: Up to 8 Weeks ]
  3. Part A: Number of participants with mature B-cell malignancies experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days posttreatment ]
  4. Part A: Number of participants with mature B-cell malignancies experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to 30 days posttreatment ]
  5. Part A: Number of participants with mature B-cell malignancies experiencing Adverse Events (AEs) Leading to Discontinuation of BGB-10188 [ Time Frame: Up to 30 days posttreatment ]
  6. Part B: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days posttreatment ]
  7. Part B: The recommended Phase 2 dose (RP2D) of BGB-10188 in combination with zanubrutinib [ Time Frame: Up to 8 Weeks ]
  8. Part B: Number of participants experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to 30 days posttreatment ]
  9. Part B: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation [ Time Frame: Up to 30 days posttreatment ]
  10. Part C: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days posttreatment ]
  11. Part C: Number of participants experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to 30 days posttreatment ]
  12. Part C: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation [ Time Frame: Up to 30 days posttreatment ]
  13. Part D: RP2D of BGB-10188 in combination with tislelizumab [ Time Frame: Up to 8 Weeks ]
  14. Part D: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days posttreatment ]
  15. Part D: Number of participants experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to 30 days posttreatment ]
  16. Part D: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation [ Time Frame: Up to 30 days posttreatment ]
  17. Part E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 30 days posttreatment ]
  18. Part E: Number of participants experiencing Severe Adverse Events (SAEs) [ Time Frame: Up to 30 days posttreatment ]
  19. Part E: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation [ Time Frame: Up to 30 days posttreatment ]

Secondary Outcome Measures :
  1. Part A: Overall response rate (ORR) [ Time Frame: 8 weeks for first 24 weeks, every 12 weeks for the next 24 weeks, and then every 16 weeks ]
    ORR is defined as the proportion of participants achieving a partial response (PR) or better

  2. Part A: Area under the plasma concentration-time curve (AUC) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  3. Part A: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  4. Part B: Overall response rate (ORR) [ Time Frame: 8 weeks for first 24 weeks, every 12 weeks for the next 24 weeks, and then every 16 weeks ]
    ORR is defined as the proportion of participants achieving a partial response (PR) or better

  5. Part B: Area under the plasma concentration-time curve (AUC) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  6. Part B: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  7. Part C: Overall response rate (ORR) [ Time Frame: 8 weeks for first 24 weeks, every 12 weeks for the next 24 weeks, and then every 16 weeks ]
    ORR is defined as the proportion of participants achieving a partial response (PR) or better

  8. Part C: Area under the plasma concentration-time curve (AUC) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  9. Part C: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  10. Part D: Overall response rate [ Time Frame: At Week 10 and every 9 weeks posttreatment ]
    ORR is defined as the proportion of participants achieving a partial response (PR) or better

  11. Part D: The preliminary anti-tumor activity of BGB-10188 in combination with tislelizumab as measured by duration of response (DOR) [ Time Frame: At Week 10 and every 9 weeks posttreatment ]
  12. Part D: The preliminary anti-tumor activity of BGB-10188 in combination with tislelizumab as measured by disease control rate (DCR) [ Time Frame: At Week 10 and every 9 weeks posttreatment ]
  13. Part D: Area under the plasma concentration-time curve (AUC) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  14. Part D: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  15. Part E: Overall response rate (ORR) [ Time Frame: At Week 10 and every 9 weeks posttreatment ]
    ORR is defined as the proportion of participants achieving a partial response (PR) or better

  16. Part E: The preliminary anti-tumor activity of BGB-10188 in combination with tislelizumab as measured by duration of response (DOR) [ Time Frame: At Week 10 and every 9 weeks posttreatment ]
  17. Part E: The preliminary anti-tumor activity of BGB-10188 in combination with tislelizumab as measured by disease control rate (DCR) [ Time Frame: At Week 10 and every 9 weeks posttreatment ]
  18. Part E: Area under the plasma concentration-time curve (AUC) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]
  19. Part E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188 [ Time Frame: Predose up to 7 days postdose ]


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:

Part A, B and C

  1. Confirmed diagnosis of one of the following:

    • Part A: R/R CLL/SLL, MZL, FL, MCL
    • Part B: R/R FL, MCL, or DLBCL
    • Part C: R/R FL, MCL, or DLBCL
  2. Patients with MZL, FL, MCL, or DLBCL must have at least one bi- dimensionally measurable nodal lesion >1.5 cm in longest diameter or extranodal lesion that is > 1cm in longest diameter by computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by the Lugano Classification.

    Part D and E

  3. Part D: Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors previously treated with standard systemic therapy or for which treatment is not available or not tolerated. Enrollment will be limited to patients 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 patient 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: Patients with NSCLC or metastatic melanoma that has progressed from PD 1/PD-L1 antibody treatment or patients with SCLC with no prior PD 1/PD-L1 antibody treatment.
  5. Part D: Patient must have at least 1 evaluable lesion (either measurable or non-measurable) as defined by RECIST v1.1.

Key Exclusion Criteria:

Part A, B and C

  1. History of allogeneic stem-cell transplantation in Part A, Part B, and Part C

    Part A, B, C, D and E

  2. Prior exposure to PI3K inhibitor.
  3. 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.
  4. 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.
  5. 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. Patients 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
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
Sponsors and Collaborators
BeiGene
Investigators
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Study Director: Yuan Liu, MD 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: September 29, 2020
Last Verified: September 2020
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
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell
Lymphoma, B-Cell
Zanubrutinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action