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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04282018
Ethics application status
Date submitted
5/02/2020
Date registered
24/02/2020
Date last updated
29/09/2020

Titles & IDs
Public title
Brief 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
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
Non-small Cell Lung Cancer 0 0
Metastatic Melanoma 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 a dose level less than RP2D and RP2D in combination with zanubrutinib 160mg (2*80mg capsules) administered orally twice daily (BID)

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

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)

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


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 maximum tolerated dose (MTD) of BGB-10188 monotherapy
Timepoint [1] 0 0
Up to 8 Weeks
Primary outcome [2] 0 0
Part A: The recommended Phase 2 dose (RP2D) of BGB-10188 monotherapy in mature B-cell malignancies
Timepoint [2] 0 0
Up to 8 Weeks
Primary outcome [3] 0 0
Part A: Number of participants with mature B-cell malignancies experiencing Treatment Emergent Adverse Events (TEAEs)
Timepoint [3] 0 0
Up to 30 days posttreatment
Primary outcome [4] 0 0
Part A: Number of participants with mature B-cell malignancies experiencing Severe Adverse Events (SAEs)
Timepoint [4] 0 0
Up to 30 days posttreatment
Primary outcome [5] 0 0
Part A: Number of participants with mature B-cell malignancies experiencing Adverse Events (AEs) Leading to Discontinuation of BGB-10188
Timepoint [5] 0 0
Up to 30 days posttreatment
Primary outcome [6] 0 0
Part B: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
Timepoint [6] 0 0
Up to 30 days posttreatment
Primary outcome [7] 0 0
Part B: The recommended Phase 2 dose (RP2D) of BGB-10188 in combination with zanubrutinib
Timepoint [7] 0 0
Up to 8 Weeks
Primary outcome [8] 0 0
Part B: Number of participants experiencing Severe Adverse Events (SAEs)
Timepoint [8] 0 0
Up to 30 days posttreatment
Primary outcome [9] 0 0
Part B: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation
Timepoint [9] 0 0
Up to 30 days posttreatment
Primary outcome [10] 0 0
Part C: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
Timepoint [10] 0 0
Up to 30 days posttreatment
Primary outcome [11] 0 0
Part C: Number of participants experiencing Severe Adverse Events (SAEs)
Timepoint [11] 0 0
Up to 30 days posttreatment
Primary outcome [12] 0 0
Part C: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation
Timepoint [12] 0 0
Up to 30 days posttreatment
Primary outcome [13] 0 0
Part D: RP2D of BGB-10188 in combination with tislelizumab
Timepoint [13] 0 0
Up to 8 Weeks
Primary outcome [14] 0 0
Part D: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
Timepoint [14] 0 0
Up to 30 days posttreatment
Primary outcome [15] 0 0
Part D: Number of participants experiencing Severe Adverse Events (SAEs)
Timepoint [15] 0 0
Up to 30 days posttreatment
Primary outcome [16] 0 0
Part D: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation
Timepoint [16] 0 0
Up to 30 days posttreatment
Primary outcome [17] 0 0
Part E: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)
Timepoint [17] 0 0
Up to 30 days posttreatment
Primary outcome [18] 0 0
Part E: Number of participants experiencing Severe Adverse Events (SAEs)
Timepoint [18] 0 0
Up to 30 days posttreatment
Primary outcome [19] 0 0
Part E: Number of participants experiencing Adverse Events (AEs) Leading to Treatment Discontinuation
Timepoint [19] 0 0
Up to 30 days posttreatment
Secondary outcome [1] 0 0
Part A: Overall response rate (ORR) - ORR is defined as the proportion of participants achieving a partial response (PR) or better
Timepoint [1] 0 0
8 weeks for first 24 weeks, every 12 weeks for the next 24 weeks, and then every 16 weeks
Secondary outcome [2] 0 0
Part A: Area under the plasma concentration-time curve (AUC) of BGB-10188
Timepoint [2] 0 0
Predose up to 7 days postdose
Secondary outcome [3] 0 0
Part A: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188
Timepoint [3] 0 0
Predose up to 7 days postdose
Secondary outcome [4] 0 0
Part B: Overall response rate (ORR) - ORR is defined as the proportion of participants achieving a partial response (PR) or better
Timepoint [4] 0 0
8 weeks for first 24 weeks, every 12 weeks for the next 24 weeks, and then every 16 weeks
Secondary outcome [5] 0 0
Part B: Area under the plasma concentration-time curve (AUC) of BGB-10188
Timepoint [5] 0 0
Predose up to 7 days postdose
Secondary outcome [6] 0 0
Part B: 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
Part C: Overall response rate (ORR) - ORR is defined as the proportion of participants achieving a partial response (PR) or better
Timepoint [7] 0 0
8 weeks for first 24 weeks, every 12 weeks for the next 24 weeks, and then every 16 weeks
Secondary outcome [8] 0 0
Part C: Area under the plasma concentration-time curve (AUC) of BGB-10188
Timepoint [8] 0 0
Predose up to 7 days postdose
Secondary outcome [9] 0 0
Part C: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188
Timepoint [9] 0 0
Predose up to 7 days postdose
Secondary outcome [10] 0 0
Part D: Overall response rate - ORR is defined as the proportion of participants achieving a partial response (PR) or better
Timepoint [10] 0 0
At Week 10 and every 9 weeks posttreatment
Secondary outcome [11] 0 0
Part D: The preliminary anti-tumor activity of BGB-10188 in combination with tislelizumab as measured by duration of response (DOR)
Timepoint [11] 0 0
At Week 10 and every 9 weeks posttreatment
Secondary outcome [12] 0 0
Part D: The preliminary anti-tumor activity of BGB-10188 in combination with tislelizumab as measured by disease control rate (DCR)
Timepoint [12] 0 0
At Week 10 and every 9 weeks posttreatment
Secondary outcome [13] 0 0
Part D: Area under the plasma concentration-time curve (AUC) of BGB-10188
Timepoint [13] 0 0
Predose up to 7 days postdose
Secondary outcome [14] 0 0
Part D: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188
Timepoint [14] 0 0
Predose up to 7 days postdose
Secondary outcome [15] 0 0
Part E: Overall response rate (ORR) - ORR is defined as the proportion of participants achieving a partial response (PR) or better
Timepoint [15] 0 0
At Week 10 and every 9 weeks posttreatment
Secondary outcome [16] 0 0
Part E: The preliminary anti-tumor activity of BGB-10188 in combination with tislelizumab as measured by duration of response (DOR)
Timepoint [16] 0 0
At Week 10 and every 9 weeks posttreatment
Secondary outcome [17] 0 0
Part E: The preliminary anti-tumor activity of BGB-10188 in combination with tislelizumab as measured by disease control rate (DCR)
Timepoint [17] 0 0
At Week 10 and every 9 weeks posttreatment
Secondary outcome [18] 0 0
Part E: Area under the plasma concentration-time curve (AUC) of BGB-10188
Timepoint [18] 0 0
Predose up to 7 days postdose
Secondary outcome [19] 0 0
Part E: Observed maximum plasma concentration during a sample interval (Cmax) of BGB-10188
Timepoint [19] 0 0
Predose up to 7 days postdose

Eligibility
Key inclusion criteria
Key

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

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Monash Hospital - Hematology - Clayton
Recruitment hospital [2] 0 0
St. Vincent Hospital - Sydney - Hematology/Oncology - Darlinghurst
Recruitment hospital [3] 0 0
Austin Hospital - Hematology - Heidelberg
Recruitment hospital [4] 0 0
Perth Blood Institute - West Perth
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Heidelberg
Recruitment postcode(s) [4] 0 0
- West Perth

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

Contacts
Principal investigator
Name 0 0
Yuan Liu, MD
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
clinicaltrials@beigene.com
Contact person for scientific queries

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