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

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Phase 1a: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Срок оценки: 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 [Срок оценки: Approximately 1 month]
• Phase 1a: RDFE of BGB-B455 [Срок оценки: Approximately 1 month]
• Phase 1b: Overall Response Rate (ORR) [Срок оценки: Approximately 18 months]

Вторичные конечные точки (12)

• Phase 1a: ORR [Срок оценки: Approximately 18 months]
• Phase 1a and 1b: Duration of Response (DOR) [Срок оценки: Approximately 18 months]
• Phase 1a and 1b: Disease Control Rate (DCR) [Срок оценки: Approximately 18 months]
• Phase 1a and 1b: Time to Response (TTR) [Срок оценки: Approximately 18 months]
• Phase 1a and 1b: Serum concentrations of BGB-B455 [Срок оценки: Approximately 7 months]
• Phase 1b: Progression-Free Survival (PFS) [Срок оценки: Approximately 18 months]
• Phase 1b: Number of participants with AEs [Срок оценки: 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 [Срок оценки: Approximately 4 months]
• Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-B455 [Срок оценки: Approximately 4 months]
• Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-B455 [Срок оценки: Approximately 4 months]
• Phase 1a and 1b: Trough Concentration (Ctrough) of BGB-B455 [Срок оценки: Approximately 7 months]
• Phase 1a and 1b: Apparent clearance (CL) of BGB-B455 [Срок оценки: Approximately 4 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 5 центров

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

Китай · 5 центров

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

Австралия · 3 центра

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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• NMPA/CDE CTR20251939 (платформа chinadrugtrials.org.cn)

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