A Study of BGB-B3227 Alone and in Combination With Tislelizumab in Participants With Advanced or Metastatic Solid Tumors

NCT06540066 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: BGB-B3227-1012024-514216-27-00CTR20244018
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 12

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.

Conditions

Advanced Cancer; Advanced Solid Tumor; Metastatic Cancer; Metastatic Solid Tumor

Keywords

BGB-B3227; tislelizumab; BGB-A317; advanced solid tumor; metastatic solid tumor

Outcome Measures

Primary Outcomes (5)

• 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 9 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 9 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 9 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 Outcomes (13)

• Phase 1a: ORR

  From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 6 months

• Phase 1b: Progression-Free Survival (PFS)

  From first dose of study drug(s) until progressive disease or new anticancer treatment; approximately 12 months

• 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

• 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

• 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

Study Arms (3)

Phase 1a Part A: Dose Escalation (BGB-B3227 Monotherapy)

EXPERIMENTAL

Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated as monotherapy.

Drug: BGB-B3227

Phase 1a Part B: Dose Escalation (BGB-B3227 + tislelizumab)

EXPERIMENTAL

Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab.

Drug: BGB-B3227; Drug: Tislelizumab

Phase 1b: Dose Expansion

EXPERIMENTAL

Sequential cohorts of increasing dose levels of BGB-B3227 will be evaluated in combination with tislelizumab and chemotherapy.

Drug: BGB-B3227; Drug: Tislelizumab; Drug: Chemotherapy

Interventions

BGB-B3227 DRUG

Administered intravenously.

Phase 1a Part A: Dose Escalation (BGB-B3227 Monotherapy); Phase 1a Part B: Dose Escalation (BGB-B3227 + tislelizumab); Phase 1b: Dose Expansion

Tislelizumab DRUG

Administered intravenously.

Also known as: BGB-A317

Phase 1a Part B: Dose Escalation (BGB-B3227 + tislelizumab); Phase 1b: Dose Expansion

Chemotherapy DRUG

Administered in accordance with relevant local guidelines and/or prescribing information.

Phase 1b: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (12)

Usc Norris Comprehensive Cancer Center (Nccc)

Los Angeles, California, 90089-1019, United States

Location

Washington University in St Louis

St Louis, Missouri, 63110-1010, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601-1915, United States

Location

Next Oncology

Austin, Texas, 78758, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030-3907, United States

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Fondazione Irccs Istituto Nazionale Dei Tumori

Milan, 20133, Italy

Location

Istituto Europeo Di Oncologia

Milan, 20141, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

tislelizumab; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2024
• First Posted: August 6, 2024
• Study Start: September 11, 2024
• Primary Completion: January 9, 2026
• Study Completion: January 9, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

IT (4); US (5); CN (3)