Phase 2
Completed N=96
Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab
Chronic Lymphocytic Leukemia · Small Lymphocytic Lymphoma · Follicular Lymphoma · Marginal Zone Lymphoma
Source: ClinicalTrials.gov NCT04282018 ↗
Enrolled (actual)
96
Serious AEs
39.6%
Results posted
Feb 2026
Primary outcomePrimary: Part A: The Recommended Dose for Expansion (RDFE) of BGB-10188 Monotherapy in Hematologic Malignancies — NA mg
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: The Recommended Dose for Expansion (RDFE) of BGB-10188 Monotherapy in Hematologic Malignancies |
NA | — |
| PRIMARY Part B: The RDFE of BGB-10188 in Combination With Zanubrutinib in Hematologic Malignancies |
NA | — |
| PRIMARY Part D: The RDFE of BGB-10188 in Combination With Tislelizumab in Advanced Solid Tumors |
320; 160 | — |
| PRIMARY Part E: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 |
0.0; 0.0 | — |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation |
4; 5; 8; 6; 10; 4 | — |
| SECONDARY Parts A and B: ORR as Assessed by Investigator |
50.0; 20.0; 50.0; 83.3; 66.7; 100 | — |
| SECONDARY Part A: Observed Maximum Plasma Concentration (Cmax) of BGB-10188 After a Single Dose |
32.9; 54.0; 332.2; 266.2; 1124.5 | — |
| SECONDARY Part A: Cmax of BGB-10188 at Steady State |
16.8; 60.7; 278.5; 205.2; 642.8 | — |
| SECONDARY Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) After Single Dose |
86.5; 277.5; 1091.9; 925.3; 3572.1 | — |
| SECONDARY Part B: Duration of Response (DOR) |
NA | — |
| SECONDARY Part B: Time to Response (TTR) |
1.69 | — |
| SECONDARY Part B: Cmax of BGB-10188 After a Single Dose |
75.9 | — |
| SECONDARY Part B: Cmax of BGB-10188 at Steady State |
89.0 | — |
| SECONDARY Part B: AUC 0-24 h of BGB-10188 After a Single Dose |
418.3 | — |
| SECONDARY Part D: Overall Response Rate (ORR) |
20.0; 20.0; 0.0; 9.1; 0.0; 14.3 | — |
| SECONDARY Parts D and E: Duration of Response (DOR) |
4.1; 8.3; NA; 6.2 | — |
| SECONDARY Parts D and E: Disease Control Rate (DCR) |
60.0; 20.0; 16.7; 36.4; 40.0; 14.3 | — |
| SECONDARY Parts D and E: Time to Response (TTR) |
2.23; 2.30; 4.24; 2.30 | — |
| SECONDARY Part D: Cmax of BGB-10188 After a Single Dose |
10.0; 12.5; 29.4; 88.8; 440.5; 811.1 | — |
| SECONDARY Part D: Cmax of BGB-10188 at Steady State |
6.2; 16.8; 74.5; 115.7; 466.9; 798.3 | — |
| SECONDARY Part D: AUC 0-24h of BGB-10188 After Single Dose |
98.0; 39.8; 110.7; 357.9; 2204.0; 4646.6 | — |
| SECONDARY Part D: AUC 0-24h of BGB-10188 at Steady State |
366.6; 153.9; 249.9; 575.9; 3448.2; 4618.5 | — |
| SECONDARY Part E: Progression-Free Survival (PFS) |
1.9; 1.9 | — |
| SECONDARY Part E: Clinical Benefit Rate (CBR) |
0.0; 0.0 | — |
| SECONDARY Part E: Cancer Antigen (CA)-125 Response Rate Per Gynecological Cancer Intergroup |
0.0; 0.0 | — |
| SECONDARY Part E: Cmax of BGB-10188 After Single Dose |
120.0; 254.5 | — |
| SECONDARY Part E: Cmax of BGB-10188 at Steady State |
232.2; 568.2 | — |
| SECONDARY Part E: AUC0-24h of BGB-10188 After Single Dose |
1106.3; 2030.5 | — |
Eligibility Criteria
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
CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma; MZL = marginal zone lymphoma
- 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
- 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.
- 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.
- Participants must have had measurable disease as assessed by RECIST v1.1.
Key Exclusion Criteria
Parts A, B and C
- History of allogeneic stem-cell transplantation or chimeric antigen receptor-T (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 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 was 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 were eligible if HCV ribonucleic acid (RNA) was undetectable
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT04282018). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.