A Study of BGB-B3227 Alone and in Combination With Tislelizumab in Participants With Advanced or Metastatic Solid Tumors
NCT Number: NCT06540066
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Advanced Cancer|Advanced Solid Tumor|Metastatic Cancer|Metastatic Solid Tumor
Interventions: DRUG: BGB-B3227|DRUG: Tislelizumab|DRUG: Chemotherapy
Sponsor: BeiGene
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 75
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-22
Completion Date: 2027-01-31

Summary:
This is a first-in-human (FIH), open-label, multicenter dose escalation and expansion study of BGB-B3227, a humanized immunoglobulin G1 (IgG1) antibody. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BGB-B3227 as a monotherapy or in combination with tislelizumab with or without chemotherapy in participants with selected advanced or metastatic solid tumors. The study will also identify recommended dose(s) for expansion (RDFE\[s\]) of BGB-B3227 administered alone and in combination with tislelizumab.

Primary Outcome Measures: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs), Number of participants with AEs and SAEs, including findings from physical examinations, laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria or protocol-defined Adverse Event of Special Interest (AESI) criteria., From first dose of the study drug(s) to 30 days after the last dose or 90 days after last dose of tislelizumab, approximately 6 months|Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD), MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached., Approximately 18 months|Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-B3227, RDFE of BGB-B3227 alone or in combination with tislelizumab will be determined based upon the MTD or MAD., Approximately 18 months|Phase 1b: Objective Response Rate (ORR), ORR is defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1., From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months|Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-B3227, RP2D established from Phase 1a for BGB-B3227 for administration in combination with tislelizumab and chemotherapy in selected tumor types., Approximately 12 months
Secondary Outcome Measures: Phase 1a: ORR, ORR is defined as the percentage of participants with confirmed best overall response of CR or PR, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1., From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 6 months|Phase 1b: Progression-Free Survival (PFS), PFS is defined as the time from the first dose of study treatment to the date of first documentation of disease progression or death, whichever occurs first, as assessed by the investigator per RECIST Version 1.1., From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months|Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events, Number of participants with AEs and SAEs, including findings from physical examinations, laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria or protocol-defined Adverse Event of Special Interest (AESI) criteria., From first dose of the study drug(s) to 30 days after the last dose, or 90 days after last dose of tislelizumab; approximately 12 months|Phase 1a and 1b: Disease Control Rate (DCR), DCR is defined as the percentage of participants who achieve confirmed CR, PR, or stable disease, as assessed by the investigator per RECIST Version 1.1., From first dose of study treatment drug(s) until confirmed response or stable disease; approximately 6 months for Phase 1a and 12 months for Phase 1b|Phase 1a and 1b: Duration of Response (DoR), DoR is defined as the time from the first confirmed objective response to disease progression documented after treatment initiation or death, whichever occurs first, as assessed by the investigator per RECIST Version 1.1., From confirmed response to disease progression or death; approximately 6 months for Phase 1a and 12 months for Phase 1b|Phase 1a and 1b: Number of Participants with Antidrug Antibodies (ADAs) against BGB-B3227, From first dose of BGB-B3227 up to 30 days after last dose of BGB-B3227; approximately 6 months for Phase 1a and 12 months for Phase 1b|Phase 1a Part B and 1b: serum concentrations of BGB-B3227, From first dose of BGB-B3227 up to 30 days after last dose of BGB-B3227; approximately 6 months for Ph1a and 12 months for Ph1b