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Trial details imported from ClinicalTrials.gov

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

Registration number

NCT04282018

Ethics application status

Date submitted

5/02/2020

Date registered

24/02/2020

Date last updated

20/02/2026

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

Additional trial identifiers [1]

CTR20220463

Additional trial identifiers [2]

BGB-A317-3111-10188-101

Universal Trial Number (UTN)

Trial acronym

Related trial records

Health condition

Health condition(s) studied:

Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

Mantle Cell Lymphoma

Diffuse Large B Cell Lymphoma

Advanced Solid Tumor

Condition category

Condition code

Cancer

Leukaemia - Chronic leukaemia

Cancer

Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Cancer

Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

Treatment: Drugs - BGB-10188
Treatment: Drugs - Zanubrutinib
Treatment: Drugs - Tislelizumab

Experimental: Part A: Dose Escalation- BGB-10188- 60 mg - Participants with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone lymphoma (MZL), follicular lymphoma (FL), mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL) received BGB-10188 60 milligrams (mg) orally, once daily (QD) from Cycle 1 day 1 (C1D1) until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

Experimental: Part A: Dose Escalation- BGB-10188- 120 mg - Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 120 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

Experimental: Part A: Dose Escalation- BGB-10188- 240 mg - Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 240 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

Experimental: Part A: Dose Escalation- BGB-10188- 360 mg - Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 360 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

Experimental: Part A: Dose Escalation- BGB-10188- 540 mg - Participants with R/R CLL/SLL, MZL, FL, MCL or DLBCL received BGB-10188 540 mg orally, QD from C1D1 until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

Experimental: Part B: Dose Escalation- BGB-10188- 240 mg + Zanubrutinib-160 mg - Participants with R/R FL, MCL, and DLBCL received BGB-10188 240 mg orally, QD from C1D1 in combination with zanubrutinib 160 mg orally, twice a day (BID) until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 28 days.

Experimental: Part D: Dose Escalation- BGB-10188- 20 mg + Tislelizumab 200 mg - Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 20 mg orally, QD from C1D1, followed by tislelizumab 200 mg intravenously (IV) on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.

Experimental: Part D: Dose Escalation- BGB-10188- 40 mg + Tislelizumab 200 mg - Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 40 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.

Experimental: Part D: Dose Escalation- BGB-10188- 80 mg + Tislelizumab 200 mg - Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 80 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.

Experimental: Part D: Dose Escalation- BGB-10188- 160 mg + Tislelizumab 200 mg - Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 160 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days, and the duration of each cycle from Cycle 2 onwards was 21 days.

Experimental: Part D: Dose Escalation- BGB-10188- 320 mg + Tislelizumab 200 mg - Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 320 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days and the duration of each cycle from Cycle 2 onwards was 21 days.

Experimental: Part D: Dose Escalation- BGB-10188- 540 mg + Tislelizumab 200 mg - Participants with unresectable locally advanced or metastatic solid tumors received BGB-10188 540 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on C1D8 and Day 1 of all subsequent cycles until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. The duration of Cycle 1 was 28 days, and the duration of each cycle from Cycle 2 onwards was 21 days.

Experimental: Part E: Dose Expansion- BGB-10188- 160 mg + Tislelizumab 200 mg - Participants with platinum-resistant ovarian cancer (PROC) were randomized to receive BGB-10188 160 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on Day 1 of each cycle until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 21 days.

Experimental: Part E: Dose Expansion- BGB-10188- 320 mg + Tislelizumab 200 mg - Participants with PROC were randomized to receive BGB-10188 320 mg orally, QD from C1D1, followed by tislelizumab 200 mg IV on Day 1 of each cycle until disease progression, unacceptable toxicity, death, withdrawal of consent, loss to follow-up, end of study, investigator's decision, or termination of the study by the sponsor, whichever occurred first. Each cycle consisted of 21 days.

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]

Treatment: Drugs

Description of the comparator or control

Control group

Outcomes

Primary outcome [1]

Part A: The Recommended Dose for Expansion (RDFE) of BGB-10188 Monotherapy in Hematologic Malignancies

Timepoint [1]

Up to 28 days

Primary outcome [2]

Part B: The RDFE of BGB-10188 in Combination With Zanubrutinib in Hematologic Malignancies

Timepoint [2]

Up to 28 days

Primary outcome [3]

Part D: The RDFE of BGB-10188 in Combination With Tislelizumab in Advanced Solid Tumors

Timepoint [3]

Up to 28 days

Primary outcome [4]

Part E: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1

Timepoint [4]

Up to 10.0 months

Primary outcome [5]

Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation

Timepoint [5]

Part A: 47.2 Months; Part B: 24 Months; Part D: 15.2 Months; Part E: 10 Months

Secondary outcome [1]

Parts A and B: ORR as Assessed by Investigator

Timepoint [1]

Part A: up to 47.2 months and Part B: up to 24 months

Secondary outcome [2]

Part A: Observed Maximum Plasma Concentration (Cmax) of BGB-10188 After a Single Dose

Timepoint [2]

Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 168 hours post-dose on Day -7 (each cycle = 28 days)

Secondary outcome [3]

Part A: Cmax of BGB-10188 at Steady State

Timepoint [3]

Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 15 (each cycle = 28 days)

Secondary outcome [4]

Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) After Single Dose

Timepoint [4]

Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8,12, and 24 hours post-dose on Day-7 (each cycle = 28 days)

Secondary outcome [5]

Part B: Duration of Response (DOR)

Timepoint [5]

Up to 24 months

Secondary outcome [6]

Part B: Time to Response (TTR)

Timepoint [6]

Up to 24 months

Secondary outcome [7]

Part B: Cmax of BGB-10188 After a Single Dose

Timepoint [7]

Pre-dose, 0.5,1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)

Secondary outcome [8]

Part B: Cmax of BGB-10188 at Steady State

Timepoint [8]

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 15 (each cycle = 28 days)

Secondary outcome [9]

Part B: AUC 0-24 h of BGB-10188 After a Single Dose

Timepoint [9]

Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)

Secondary outcome [10]

Part D: Overall Response Rate (ORR)

Timepoint [10]

Up to 15.2 months

Secondary outcome [11]

Parts D and E: Duration of Response (DOR)

Timepoint [11]

Part D: up to 15.2 months and Part E: up to 10.0 months

Secondary outcome [12]

Parts D and E: Disease Control Rate (DCR)

Timepoint [12]

Part D: up to 15.2 months and Part E: up to 10.0 months

Secondary outcome [13]

Parts D and E: Time to Response (TTR)

Timepoint [13]

Part D: up to 15.2 months and Part E: up to 10.0 months

Secondary outcome [14]

Part D: Cmax of BGB-10188 After a Single Dose

Timepoint [14]

Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)

Secondary outcome [15]

Part D: Cmax of BGB-10188 at Steady State

Timepoint [15]

Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)

Secondary outcome [16]

Part D: AUC 0-24h of BGB-10188 After Single Dose

Timepoint [16]

Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 1 Day 1 (each cycle = 28 days)

Secondary outcome [17]

Part D: AUC 0-24h of BGB-10188 at Steady State

Timepoint [17]

Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)

Secondary outcome [18]

Part E: Progression-Free Survival (PFS)

Timepoint [18]

Up to 10.0 months

Secondary outcome [19]

Part E: Clinical Benefit Rate (CBR)

Timepoint [19]

Up to 10.0 months

Secondary outcome [20]

Part E: Cancer Antigen (CA)-125 Response Rate Per Gynecological Cancer Intergroup

Timepoint [20]

Up to 10.0 months

Secondary outcome [21]

Part E: Cmax of BGB-10188 After Single Dose

Timepoint [21]

Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 1 Day 1 (each cycle = 21 days)

Secondary outcome [22]

Part E: Cmax of BGB-10188 at Steady State

Timepoint [22]

Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose on Cycle 2 Day 1 (each cycle = 21 days)

Secondary outcome [23]

Part E: AUC0-24h of BGB-10188 After Single Dose

Timepoint [23]

Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose of Cycle 1 Day 1 (each cycle = 21 days)

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 had at least one bi-dimensionally measurable nodal lesion greater than (>) 1.5 centimeters (cm) in the longest diameter or extranodal lesion that is > 1 cm 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 was limited to participants with advanced solid tumors for which there was clinical evidence of response to T-cell based immuno-oncology agents (e.g., 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 required 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 have been platinum resistant and checkpoint inhibitor (CPI) naïve.
5. Participants must have had measurable disease as assessed by RECIST v1.1.

Key

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Healthy volunteers

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 was 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 were eligible if HCV ribonucleic acid (RNA) was 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

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

29/04/2020

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

28/08/2024

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,VIC,WA

Recruitment hospital [1]

Blacktown Cancer and Haematology Centre - Blacktown

Recruitment hospital [2]

Saint Vincents Hospital Sydney - Darlinghurst

Recruitment hospital [3]

Pindara Private Hospital - Benowa

Recruitment hospital [4]

Gallipoli Medical Research Foundation - Greenslopes

Recruitment hospital [5]

Royal Adelaide Hospital - Adelaide

Recruitment hospital [6]

Monash Health - Clayton

Recruitment hospital [7]

Austin Health - Heidelberg

Recruitment hospital [8]

Perth Blood Institute - West Perth

Recruitment postcode(s) [1]

2148 - Blacktown

Recruitment postcode(s) [2]

2010 - Darlinghurst

Recruitment postcode(s) [3]

4217 - Benowa

Recruitment postcode(s) [4]

4120 - Greenslopes

Recruitment postcode(s) [5]

5000 - Adelaide

Recruitment postcode(s) [6]

3168 - Clayton

Recruitment postcode(s) [7]

3084 - Heidelberg

Recruitment postcode(s) [8]

6005 - West Perth

Recruitment outside Australia

Country [1]

China

State/province [1]

Beijing Municipality

Country [2]

China

State/province [2]

Fujian

Country [3]

China

State/province [3]

Guangdong

Country [4]

China

State/province [4]

Henan

Country [5]

China

State/province [5]

Hubei

Country [6]

China

State/province [6]

Hunan

Country [7]

China

State/province [7]

Jiangsu

Country [8]

China

State/province [8]

Jilin

Country [9]

China

State/province [9]

Ningxia

Country [10]

China

State/province [10]

Shandong

Country [11]

China

State/province [11]

Shanghai Municipality

Country [12]

China

State/province [12]

Sichuan

Country [13]

China

State/province [13]

Zhejiang

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 was 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/study/NCT04282018

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Study Director

Address

BeiGene

Country

Phone

Fax

Contact person for public queries

Name

BeiGene

Address

Country

Phone

1-877-828-5568

Fax

[email protected]

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)

When will data be available (start and end dates)?

See plan description

Available to whom?

See plan description

Available for what types of analyses?

How or where can data be obtained?

IPD available at link: https://beigene.com/science/clinical-trials/

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol		https://cdn.clinicaltrials.gov/large-docs/18/NCT04282018/Prot_000.pdf
Statistical analysis plan		https://cdn.clinicaltrials.gov/large-docs/18/NCT04282018/SAP_001.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04282018

Trial Review

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