Clinical trial NCT06540066: A Study of BGB-B3227 Alone and in Combination With Tislelizumab in Participants With Advanced or Metastatic Solid Tumors
Official title: A Multicenter, Open-label, Phase 1a/1b Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B3227 as Monotherapy and in Combination With Tislelizumab in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Cancer
Advanced Solid Tumor
Metastatic Cancer
Metastatic Solid Tumor
Keywords: BGB-B3227
tislelizumab
BGB-A317
advanced solid tumor
metastatic solid tumor
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-08-06
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 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
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
timeFrame: Approximately 9 months
measure: Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-B3227
timeFrame: Approximately 9 months
measure: Phase 1b: Objective Response Rate (ORR)
timeFrame: From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months
measure: Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-B3227
timeFrame: Approximately 12 months
Secondary outcomes:
measure: Phase 1a: ORR
timeFrame: From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 6 months
measure: Phase 1b: Progression-Free Survival (PFS)
timeFrame: From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months
measure: Phase 1b: Number of Participants with AEs and SAEs
timeFrame: 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
measure: Phase 1a and 1b: Disease Control Rate (DCR)
timeFrame: 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
measure: Phase 1a and 1b: Duration of Response (DoR)
timeFrame: From confirmed response to disease progression or death; approximately 6 months for Phase 1a and 12 months for Phase 1b
measure: Phase 1a and 1b: Serum Concentrations of BGB-B3227
timeFrame: 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
measure: Phase 1a and 1b: Number of Participants with Antidrug Antibodies (ADAs) against BGB-B3227
timeFrame: 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
measure: Phase 1a: Area under the Curve (AUC) of BGB-B3227
timeFrame: Approximately 4 months
measure: Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-B3227
timeFrame: Approximately 4 months
measure: Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-B3227
timeFrame: Approximately 4 months
measure: Phase 1a: Trough concentration (Ctrough) of BGB-B3227
timeFrame: Approximately 4 months
measure: Phase 1a: Accumulation ratio of BGB-B3227
timeFrame: Approximately 4 months
measure: Phase 1a: Terminal half-life (t1/2) of BGB-B3227
timeFrame: Approximately 4 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center (Nccc)
state: California
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Milano
country: Italy
facility: Fondazione Irccs Istituto Nazionale Dei Tumori
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: