Trial Review

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04282018




Registration number
NCT04282018
Ethics application status
Date submitted
5/02/2020
Date registered
24/02/2020
Date last updated
7/06/2024

Titles & IDs
Public title
Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab
Scientific title
A Phase 1/2, Dose Escalation and Expansion Study of BGB-10188, a Phosphatidylinositol 3-Kinase Delta (PI3Kd) Inhibitor, Combined With Zanubrutinib in Patients With Mature B-Cell Malignancies and Combined With Tislelizumab in Patients With Solid Tumors
Secondary ID [1] 0 0
CTR20220463
Secondary ID [2] 0 0
BGB-A317-3111-10188-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Follicular Lymphoma 0 0
Marginal Zone Lymphoma 0 0
Mantle Cell Lymphoma 0 0
Diffuse Large B Cell Lymphoma 0 0
Advanced Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BGB-10188
Treatment: Drugs - Zanubrutinib
Treatment: Drugs - Tislelizumab

Experimental: Part A: BGB-10188 Monotherapy Dose Escalation - BGB-10188 capsules administered orally once daily (QD) in 5 cohorts of escalating doses

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)

Experimental: Part C: BGB-10188 + Zanubrutinib Dose Expansion - This Part was originally planned but was cancelled by the sponsor and will not be initiated.

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)

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


Treatment: Drugs: BGB-10188
Administered as specified in the treatment arm

Treatment: Drugs: Zanubrutinib
Administered as specified in the treatment arm

Treatment: Drugs: Tislelizumab
Administered as specified in the treatment arm
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: The recommended dose for expansion (RDFE) of BGB-10188 monotherapy
Timepoint [1] 0 0
Up to 8 Weeks
Primary outcome [2] 0 0
Part B: RDFE of BGB-10188 in combination with zanubrutinib
Timepoint [2] 0 0
Up to 8 Weeks
Primary outcome [3] 0 0
Part D: RDFE of BGB-10188 in combination with tislelizumab
Timepoint [3] 0 0
Up to 8 Weeks
Primary outcome [4] 0 0
Part E: Overall response rate (ORR)
Timepoint [4] 0 0
Up to approximately 5 years and 6 months
Primary outcome [5] 0 0
Parts A, B, D, and E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
Timepoint [5] 0 0
Up to approximately 5 years and 6 months
Primary outcome [6] 0 0
Parts A, B, D, and E: Number of participants experiencing Severe Adverse Events (SAEs)
Timepoint [6] 0 0
Up to approximately 5 years and 6 months
Primary outcome [7] 0 0
Parts A, B, D and E: Number of participants experiencing Adverse Events (AEs) Leading to Discontinuation
Timepoint [7] 0 0
Up to approximately 5 years and 6 months
Secondary outcome [1] 0 0
Parts A, B, and D: Overall response rate (ORR)
Timepoint [1] 0 0
Up to approximately 5 years and 6 months
Secondary outcome [2] 0 0
Parts B, D, and E: Duration of response (DOR)
Timepoint [2] 0 0
Up to approximately 5 years and 6 months
Secondary outcome [3] 0 0
Parts B, D, and E: Time to response (TTR)
Timepoint [3] 0 0
Up to approximately 5 years and 6 months
Secondary outcome [4] 0 0
Part E: Progression-free survival (PFS)
Timepoint [4] 0 0
Up to approximately 5 years and 6 months
Secondary outcome [5] 0 0
Parts D and E: Disease control rate (DCR)
Timepoint [5] 0 0
Up to approximately 5 years and 6 months
Secondary outcome [6] 0 0
Parts A, B, D, and E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188
Timepoint [6] 0 0
Predose up to 7 days postdose
Secondary outcome [7] 0 0
Parts A, B, D, and E: Area under the plasma concentration-time curve (AUC) of BGB-10188
Timepoint [7] 0 0
Predose up to 7 days postdose
Secondary outcome [8] 0 0
Part E: Clinical Benefit Rate (CBR)
Timepoint [8] 0 0
Up to approximately 5 years and 6 months
Secondary outcome [9] 0 0
Part E: CA-125 Response Rate
Timepoint [9] 0 0
Up to approximately 5 years and 6 months

Eligibility
Key inclusion criteria
Key

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 CLL = chronic lymphocytic leukemia; SLL =
small lymphocytic lymphoma; MZL = marginal zone lymphoma

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/05/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
113
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Blacktown Cancer and Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
Saint Vincents Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [4] 0 0
Gallipoli Medical Research Foundation - Greenslopes
Recruitment hospital [5] 0 0
Monash Health - Clayton
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
4217 - Benowa
Recruitment postcode(s) [4] 0 0
4120 - Greenslopes
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
China
State/province [1] 0 0
Beijing
Country [2] 0 0
China
State/province [2] 0 0
Henan
Country [3] 0 0
China
State/province [3] 0 0
Hubei
Country [4] 0 0
China
State/province [4] 0 0
Jilin
Country [5] 0 0
China
State/province [5] 0 0
Ningxia
Country [6] 0 0
China
State/province [6] 0 0
Shandong
Country [7] 0 0
China
State/province [7] 0 0
Shanghai

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04282018
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BeiGene
Address 0 0
Country 0 0
Phone 0 0
1-877-828-5568
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04282018