Trial Outcomes & Findings for Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab (NCT NCT04282018)

A total of 97 participants were enrolled, out of which 96 were randomized and treated. One participant was enrolled but not treated. Part C was cancelled by the sponsor and not initiated.

Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab

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.

ORR was defined as the percentage of participants who had CR or PR as determined from investigator-derived tumor assessments per RECIST v. 1.1. 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 \< 10 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.

Cmax of BGB-10188 after a single dose was determined.

Cmax of BGB-10188 at steady state was determined.

Area under the plasma concentration-time curve of BGB-10188 from time 0 to 24 hours (AUC0-24) was determined.

DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of progression (PD) or death, whichever came first. Median DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., 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 \< 10 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. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

TRR was defined as the time from treatment initiation to the first documentation of response. 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 a reduction in short axis to \< 10 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.

Cmax of BGB-10188 after a single dose when given in combination with zanubrutinib was determined.

Cmax of BGB-10188 at steady state when given in combination with zanubrutinib was determined.

AUC 0-24 h of BGB-10188 after a single dose when given in combination with zanubrutinib was determined.

ORR was defined as the percentage of participants who had CR or PR as determined from investigator-derived tumor assessments per RECIST v. 1.1. 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 \< 10 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.

DOR was defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of PD or death, whichever came first. Median DOR was estimated using the Kaplan-Meier method. Per RECIST v1.1., 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 \< 10 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. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment.

DCR was defined as the percentage of participants with best overall response (BOR), as per RECIST v.1.1, of a CR, PR, or stable disease (SD). 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 \< 10 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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

TTR was defined as the time from treatment initiation to the first documentation of response. 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 a reduction in short axis to \< 10 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.

Cmax of BGB-10188 after a single dose when given in combination with tislelizumab was determined.

Cmax of BGB-10188 at steady state when given in combination with tislelizumab was determined.

AUC 0-24 h of BGB-10188 after a single dose when given in combination with tislelizumab was determined.

AUC 0-24 h of BGB-10188 at steady state when given in combination with tislelizumab was determined.

PFS was defined as the time from the date of the first dose of study drugs to the date of the first documentation of PD assessed by the investigator using RECIST v1.1 or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

CBR was defined as the percentage of participants with best overall response, as defined by RECIST v1.1, of a CR, PR, or at least 24 weeks of SD. 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 \< 10 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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

CA-125 response rate was defined as the percentage of participants achieving a CA-125 response according to the Gynecological Cancer Center Intergroup criteria, in which a response had occurred if there was at least a 50% reduction in CA-125 levels from baseline.

Cmax of BGB-10188 after a single dose when given in combination with tislelizumab was determined.

Cmax of BGB-10188 at steady state when given in combination with tislelizumab was determined.

AUC0-24 h of BGB-10188 after a single dose when given in combination with tislelizumab was determined.