A Study of BGB-R046 as Monotherapy and in Combination With Tislelizumab in Solid Tumors
NCT Number: NCT06487858
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Solid Tumor
Interventions: DRUG: BGB-R046|DRUG: Tislelizumab
Sponsor: BeiGene
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 74
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-16
Completion Date: 2027-12
Locations: Fujian Cancer Hospital, Fuzhou, Fujian, 350014, China|Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China

Summary:
This is a first-in-human (FIH) study that will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-R046 as a single agent and in combination with tislelizumab (BGB-A317) in participants with advanced or metastatic immune-sensitive solid tumors.

Primary Outcome Measures: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Number of participants with AEs including serious adverse events (SAEs), defined as any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease temporally associated with the use of study drugs, whether considered related to study drugs or not as graded by the National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI CTCAE) V5.0/American Society for Transplantation and Cellular Therapy (ASTCT) for cytokine release syndrome \[CRS\] and immune effector cell associated neurotoxicity syndrome \[ICANS\]), Up to approximately 2 years|Phase 1a: Maximum Tolerated Dose (MTD) of BGB-R046, MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% or the highest dose administered, respectively, Up to approximately 2 years|Phase 1a: Maximum Administered Dose (MAD) of BGB-R046, MAD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30% or the highest dose administered, respectively, Up to approximately 2 years|Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-R046, The potential RDFE\[s\] of BGB-R046 administered as monotherapy and in combination with tislelizumab will be determined based on the totality of the data and will also take in consideration the long term tolerability, pharmacokinetics, preliminary antitumor activity and any other relevant data available, Up to approximately 2 years|Phase 1b: Overall Response Rate (ORR), ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) as determined by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Up to approximately 2 years
Secondary Outcome Measures: Phase 1a: ORR, ORR is defined as the percentage of participants with confirmed CR or PR as determined by investigators per RECIST v1.1, Up to approximately 2 years|Phase 1a: Time to Response (TTR), TTR is defined as the time from the date of the first dose of study drug(s) to the date of the first determination of overall response by the investigator using RECIST v1.1, Up to approximately 2 years|Phase 1a: Clinical Benefit Rate (CBR), CBR is defined as the proportion of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks, Up to approximately 2 years|Phase 1a and Phase 1b: Duration of Response (DOR), DOR is defined as the time from the first objective response until the first documentation of disease progression after treatment initiation or death, whichever comes first, as determined by investigators per RECIST v1.1, Up to approximately 2 years|Phase 1a and Phase 1b: Disease Control Rate (DCR), DCR is defined as the proportion of participants with the best overall response (BOR) of confirmed CR, PR, or stable disease, as determined by investigators per RECIST v1.1, Up to approximately 2 years|Phase 1b: Progression-free survival (PFS), PFS is defined as the time from the date of the first administration of study drug to the date of the first documentation of disease progression or death due to any cause, whichever occurs first, as determined by investigators per RECIST v1.1, Up to approximately 2 years|Phase 1b: Number of Participants with Adverse Events (AEs), Number of participants with AEs, including serious adverse events (SAEs), defined as any unfavorable and unintended sign (including abnormal laboratory findings, physical examination, or electrocardiogram results), symptom, or disease temporally associated with the use of study drugs, whether considered related to study drugs or not as graded by NCI-CTCAE V5.0 or ASTCT as appropriate, Up to approximately 2 years|Phase 1a: Plasma concentrations of BGB-R046 analytes, Predose and at select time points in Cycles 1, 2 and 5; predose at select Cycles between Cycles 3 and 25 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days [± 7 days] after the last dose of study drug)|Phase 1b: Plasma concentrations of BGB-R046 analytes, Predose and after end of infusion in Cycles 1 and 5; predose at select Cycles between Cycles 1 and 25 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days [± 7 days] after the last dose of study drug)|Phase 1b: Plasma concentrations of tislelizumab, Predose and after end of infusion in Cycles 1 and 5; predose at select Cycles between Cycles 1 and 17 (each cycle is 21 days); and at the first safety follow-up visit (conducted 30 days [± 7 days] after the last dose of study drug)|Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-R046, Cycle 1 and Cycle 5 (each cycle is 21 days)|Phase 1a and 1b: Minimum Observed Plasma Concentration (Ctrough) Of BGB-R046, Cycle 1 and Cycle 5 (each cycle is 21 days)|Phase 1a and 1b: Area Under the Plasma Concentration-time Curve (AUC) of BGB-R046, Cycle 1 and Cycle 5 (each cycle is 21 days)|Phase 1a and 1b: Terminal Half-Life (t1/2) of BGB-R046, Cycle 1 and Cycle 5 (each cycle is 21 days)|Phase 1a and 1b: Incidence of Antidrug Antibodies (ADAs) to BGB-R046 and tislelizumab, Periodic sampling up to Cycle 25 (each cycle is 21 days) and at the first safety follow up visit up to approximately 2 years (conducted 30 days [± 7 days] after the last dose of study drug)