A Study of BGB-B3227 Alone and in Combination With Tislelizumab in Participants With Advanced or Metastatic Solid Tumors
- Conditions
- Advanced CancerMetastatic Solid TumorAdvanced Solid TumorMetastatic Cancer
- Interventions
- Registration Number
- NCT06540066
- Lead Sponsor
- BeiGene
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
- Histologically or cytologically confirmed locally advanced or metastatic solid tumors with a high prevalence of mucin-1 (MUC1) expression
- At least 1 measurable lesion per RECIST v1.1
- Stable Eastern Cooperative Oncology Group Performance Status of ≤ 1
- Adequate organ function
- Willing to use a highly effective method of birth control
- History of prior ≥ Grade 3 Cytokine Release Syndrome (CRS)
- History of severe Infusion-Related Reactions (IRRs), allergic reactions, or hypersensitivity to any ingredients or components of the study treatments
- Infection requiring systemic (oral or intravenous) therapy ≤ 14 days before the first dose of study drug(s), or participants with symptomatic COVID-19 infection
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis
- Active autoimmune disease or history of autoimmune disease(s) that may relapse
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a Part A: Dose Escalation (BGB-B3227 Monotherapy) BGB-B3227 Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated as monotherapy. Phase 1a Part B: Dose Escalation (BGB-B3227 + tislelizumab) Tislelizumab Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab. Phase 1b: Dose Expansion Tislelizumab Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab and chemotherapy. Phase 1b: Dose Expansion Chemotherapy Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab and chemotherapy. Phase 1a Part B: Dose Escalation (BGB-B3227 + tislelizumab) BGB-B3227 Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab. Phase 1b: Dose Expansion BGB-B3227 Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab and chemotherapy.
- Primary Outcome Measures
Name Time Method Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) From first dose of the study drug(s) to 30 days after the last dose or 90 days after last dose of tislelizumab, approximately 9 months 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.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) Approximately 9 months 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.
Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-B3227 Approximately 9 months RDFE of BGB-B3227 alone or in combination with tislelizumab will be determined based upon the MTD or MAD.
Phase 1b: Objective Response Rate (ORR) From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months 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.
Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-B3227 Approximately 12 months RP2D established from Phase 1a for BGB-B3227 for administration in combination with tislelizumab and chemotherapy in selected tumor types.
- Secondary Outcome Measures
Name Time Method Phase 1a: ORR From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 6 months 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.
Phase 1b: Progression-Free Survival (PFS) From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months 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.
Phase 1b: Number of Participants with AEs and SAEs 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 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.
Phase 1a and 1b: Disease Control Rate (DCR) 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 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.
Phase 1a and 1b: Duration of Response (DoR) From confirmed response to disease progression or death; approximately 6 months for Phase 1a and 12 months for Phase 1b 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.
Phase 1a 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 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: Area under the Curve (AUC) of BGB-B3227 Approximately 4 months Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-B3227 Approximately 4 months Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-B3227 Approximately 4 months Phase 1a: Trough concentration (Ctrough) of BGB-B3227 Approximately 4 months Phase 1a: Accumulation ratio of BGB-B3227 Approximately 4 months Phase 1a: Terminal half-life (t1/2) of BGB-B3227 Approximately 4 months
Trial Locations
- Locations (12)
Usc Norris Comprehensive Cancer Center (Nccc)
🇺🇸Los Angeles, California, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Washington University in St Louis
🇺🇸Saint Louis, Missouri, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Next Oncology
🇺🇸San Antonio, Texas, United States
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Fondazione Irccs Istituto Nazionale Dei Tumori
🇮🇹Milano, Italy
Istituto Europeo Di Oncologia
🇮🇹Milano, Italy
Fondazione Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy