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

Sponsor

BeiGene (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04282018

Collaborator

(none)

150

Enrollment

Locations

Arms

65.4

Anticipated Duration (Months)

12.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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

Anticipated Primary Completion Date :

Mar 26, 2025

Anticipated Study Completion Date :

Nov 7, 2025

Arms and Interventions

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 5 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 Names: 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 Names: BGB-A317

Outcome Measures

Primary Outcome Measures

Part A: The recommended Phase 2 dose (RP2D) of BGB-10188 monotherapy [Up to 8 Weeks]
Part B: RP2D of BGB-10188 in combination with zanubrutinib [Up to 8 Weeks]
Part D: RP2D of BGB-10188 in combination with tislelizumab [Up to 8 Weeks]
Part C and E: Overall response rate (ORR) [Up to approximately 5 years and 6 months]
ORR is defined as the proportion of participants achieving a partial response (PR) or better
Parts A, B, and D: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [Up to approximately 5 years and 6 months]
Parts A, B, and D: Number of participants experiencing Severe Adverse Events (SAEs) [Up to approximately 5 years and 6 months]
Parts A, B and D: Number of participants experiencing Adverse Events (AEs) Leading to Discontinuation [Up to approximately 5 years and 6 months]

Secondary Outcome Measures

Parts A, B, and D: Overall response rate (ORR) [Up to approximately 5 years and 6 months]
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) [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
Parts B, C, D, and E: Time to response (TTR) [Up to approximately 5 years and 6 months]
TTR is defined as the time from treatment initiation to the first documentation of response
Parts C and E: Progression-free survival (PFS) [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
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]
Parts C and E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs) [Up to approximately 5 years and 6 months]
Parts C and E: Number of participants experiencing Severe Adverse Events (SAEs) [Up to approximately 5 years and 6 months]
Parts C and E: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation [Up to approximately 5 years and 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Key Exclusion Criteria:

Parts A, B and C

History of allogeneic stem-cell transplantation or 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 (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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	a) Hematology and Bone Marrow Transplant Unit, Royal Adelaide Hospital,	Adelaide		Australia	5000
2	Blacktown Hospital	Blacktown		Australia	2148
3	Monash Hospital - Hematology	Clayton		Australia
4	St. Vincent Hospital - Sydney - Hematology/Oncology	Darlinghurst		Australia
5	Austin Hospital - Hematology	Heidelberg		Australia
6	Royal Brisbane and Women's Hospital	Herston		Australia	4029
7	Perth Blood Institute	West Perth		Australia
8	Second Affiliated Hospital of Zhejiang University School of Medicine	Zhejiang	Hangzhou	China	310009
9	Third Xiangya Hospital of Central South University	Changsha	Hunan	China
10	First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China
11	Fudan University Zhongshan Hospital	Shanghai	Shanghai	China	200032
12	West China Hospital	Chengdu	Sichuan	China	610041