Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04282018 | Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab | PHASE1 | COMPLETED | 97 | — | — | Apr 29, 2020 | Aug 28, 2024 | Feb 20, 2026 | 24 | Australia, China |
The RDFE of BGB-10188 monotherapy in participants with hematologic malignancies was planned to be determined from safety, tolerability, pharmacokinetic (PK), and any other relevant and available data based on recommendations from the Safety Monitoring Committee. Part A dose-escalation enrolled participants with R/R CLL/SLL, MZL, FL, MCL, and DLBCL up to 540 mg, however the maximum tolerated dose was not reached and the RDFE could not be determined based on the data that were collected.
The RDFE of BGB-10188 in combination with zanubrutinib was planned to be determined from safety, tolerability, PK, and any other relevant and available data obtained, based on recommendation of the Safety Monitoring Committee. The RDFE could not be determined since not all planned dose cohorts in this part of the study were enrolled and not enough data were collected to establish the RDFE.
The RDFE of BGB-10188 in combination with tislelizumab was determined based on the totality of safety, tolerability, PK, and any other relevant and available data that were obtained from the dose escalation phase for Part E.
ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR). Per RECIST v.1.1., CR was defined as disappearance of all target lesions, non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
An AE was defined as any unfavorable and unintended sign, symptom, or disease associated with the use of study drugs, whether considered related to study drugs or not. An SAE was any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly or was considered a medically significant. TEAE was an AE that has an onset date or a worsening in severity from baseline on or after the first dose of study drug. Severity of AEs was assessed according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v.5.0, which consists of: Grade 1 Mild; Grade 2 Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death due to AE.
| Arm | Type | Description |
|---|---|---|
| Part A: Dose Escalation- BGB-10188- 60 mg | EXPERIMENTAL | 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. |
| Part A: Dose Escalation- BGB-10188- 120 mg | EXPERIMENTAL | 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. |
| Part A: Dose Escalation- BGB-10188- 240 mg | EXPERIMENTAL | 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. |
| Part A: Dose Escalation- BGB-10188- 360 mg | EXPERIMENTAL | 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. |
| Part A: Dose Escalation- BGB-10188- 540 mg | EXPERIMENTAL | 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. |
| Part B: Dose Escalation- BGB-10188- 240 mg + Zanubrutinib-160 mg | EXPERIMENTAL | 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. |
| Part D: Dose Escalation- BGB-10188- 20 mg + Tislelizumab 200 mg | EXPERIMENTAL | 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. |
| Part D: Dose Escalation- BGB-10188- 40 mg + Tislelizumab 200 mg | EXPERIMENTAL | 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. |
| Part D: Dose Escalation- BGB-10188- 80 mg + Tislelizumab 200 mg | EXPERIMENTAL | 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. |
| Part D: Dose Escalation- BGB-10188- 160 mg + Tislelizumab 200 mg | EXPERIMENTAL | 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. |
| Part D: Dose Escalation- BGB-10188- 320 mg + Tislelizumab 200 mg | EXPERIMENTAL | 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. |
| Part D: Dose Escalation- BGB-10188- 540 mg + Tislelizumab 200 mg | EXPERIMENTAL | 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. |
| Part E: Dose Expansion- BGB-10188- 160 mg + Tislelizumab 200 mg | EXPERIMENTAL | 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. |
| Part E: Dose Expansion- BGB-10188- 320 mg + Tislelizumab 200 mg | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| BGB-10188 | DRUG | Administered as specified in the treatment arm |
| Zanubrutinib | DRUG | Administered as specified in the treatment arm |
| Tislelizumab | DRUG | Administered as specified in the treatment arm |
Key Inclusion Criteria: 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 lympho...