A Study of BGB-B455 in Adults With Advanced or Metastatic Solid Tumors

Official title

A Phase 1, Open-Label Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B455 in Patients With Selected Advanced or Metastatic Solid Tumors

Overview

The goal of this clinical trial is to learn if BGB-B455 can treat advanced or metastatic solid tumors expressing claudin 6 (CLDN6), a protein that is found on some tumors. The main questions it aims to answer are: * What is the recommended dosing for BGB-B455? * What medical problems do participants have when taking BGB-B455? The study has two parts: * Phase 1a: dose escalation and safety expansion * Phase 1b: dose expansion

Detailed description

Claudin proteins are cell proteins that can play an important role in how cancer starts and progresses. Because of its preferential expression in tumors compared to normal tissues, CLDN6 is an ideal tumor antigen to target for treatment. BGB-B455 is a bispecific antibody (BsAbs) that targets CLDN6 on tumor cells and the CD3 receptor on T cells, which may provide a CLDN6-dependent antitumor immune response in a more tolerable manner without undue systemic toxicity.

This new study will check how safe and helpful this potential anticancer drug is. In addition, this study will explore the recommended dosing level for BGB-B455. This drug will be tested by itself or in combination with investigator-selected chemotherapy in participants with selected solid tumors expressing the CLDN6 protein.

This study is an open label study, meaning that both you and your study doctor will know what study drug/treatment you are given. This study has two parts:

* Phase 1a consists of a dose escalation part where increasing amounts of the study treatment are given to different dose cohorts, and a safety expansion part that will enroll additional participants at selected doses for further assessments. * Phase 1b (dose expansion) will enroll participants at the best dose found in Phase 1a to see if it helps people with certain solid tumors.

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Interventions

• Drug BGB-B455
  Planned doses administered on specified days per protocol.
• Drug Chemotherapy
  Administered in accordance with relevant local guidelines and/or prescribing information.

Primary outcome measures

• Phase 1a: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Time frame: From the first dose of study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 7 months]
• Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B455 [Time frame: Approximately 1 month]
• Phase 1a: RDFE of BGB-B455 [Time frame: Approximately 1 month]
• Phase 1b: Overall Response Rate (ORR) [Time frame: Approximately 18 months]

Secondary outcome measures (12)

• Phase 1a: ORR [Time frame: Approximately 18 months]
• Phase 1a and 1b: Duration of Response (DOR) [Time frame: Approximately 18 months]
• Phase 1a and 1b: Disease Control Rate (DCR) [Time frame: Approximately 18 months]
• Phase 1a and 1b: Time to Response (TTR) [Time frame: Approximately 18 months]
• Phase 1a and 1b: Serum concentrations of BGB-B455 [Time frame: Approximately 7 months]
• Phase 1b: Progression-Free Survival (PFS) [Time frame: Approximately 18 months]
• Phase 1b: Number of participants with AEs [Time frame: From the first dose of study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first; up to approximately 7 months]
• Phase 1a and 1b: Area under the concentration-time curve (AUC) of BGB-B455 [Time frame: Approximately 4 months]
• Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-B455 [Time frame: Approximately 4 months]
• Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-B455 [Time frame: Approximately 4 months]
• Phase 1a and 1b: Trough Concentration (Ctrough) of BGB-B455 [Time frame: Approximately 7 months]
• Phase 1a and 1b: Apparent clearance (CL) of BGB-B455 [Time frame: Approximately 4 months]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed advanced or metastatic, and unresectable solid tumors who have previously received standard systemic therapy for advanced or metastatic disease or for whom treatment is not available or not tolerated. Only participants with CLDN6+ high-grade OC (ie, ovarian cancer, fallopian tube cancer, or primary peritoneal cancer) will be enrolled in dose escalation cohorts, starting from Protocol Amendment 3.0.
• Agreement for collection of formalin-fixed paraffin-embedded (FFPE) tumor tissue for central CLDN6 testing and other biomarker assessments.
• Tumor CLDN6 expression (CDLN6+) by central immunohistochemistry testing is required for certain cohorts.
• ≥ 1 measurable lesion as assessed by RECIST v1.1.
• Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate organ function.

Exclusion criteria

• Prior systemic anticancer therapy, including chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin), targeted therapy, and antibody drug conjugates (ADCs) that are standard or investigational agents (including herbal medicine or Chinese \[or other country\] patent medicines, ≤ 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug(s).
• Palliative radiation treatment or other locoregional therapies ≤ 14 days before the first dose of study drug(s).
• Live vaccine ≤ 28 days before the first dose of study drug(s). Vaccines for COVID-19 are allowed except for any live vaccine that may become available. Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.
• Any major surgical procedure ≤ 28 days before the first dose of study drug(s).
• History of prior ≥ Grade 3 cytokine release syndrome (CRS).
• Participants with toxicities (because of prior anticancer therapy) that have not recovered to baseline or stabilized, except for adverse events not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• Adventhealth — Celebration
• Sidney Kimmel Cancer Center — Philadelphia
• Avera Cancer Institute — Sioux Falls
• Next Oncology — San Antonio
• Fred Hutchinson Cancer Research Center — Seattle

China · 5 centers

• Beijing Cancer Hospital — Beijing
• Sun Yat Sen University Cancer Center — Guangzhou
• The First Affiliated Hospital of Nanchang University Branch Donghu — Nanchang
• Fudan University Shanghai Cancer Centerpudong — Shanghai
• Shanxi Provincial Cancer Hospital — Taiyuan

Australia · 3 centers

• Blacktown Cancer and Haematology Centre — Blacktown
• Liverpool Hospital — Liverpool
• Mater Cancer Care Centre — South Brisbane

Identifiers

NCT: NCT06803680 · BGB-B455-101 · 2024-512931-64-00 · CTR20251939

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20251939 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗