A Phase 1 Study of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Advanced or Metastatic Solid Tumors

Официальное название

A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-B2033, Alone or in Combination With Tislelizumab With or Without Bevacizumab, in Participants With Selected Advanced or Metastatic Solid Tumors

Обзор

This is a first-in-human (FIH) clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of BGB-B2033 administered as monotherapy and in combination with tislelizumab, with or without bevacizumab. The study will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP)-producing gastric cancer (GC), extragonadal yolk sac tumors/non-dysgerminomas, or glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC).

Вмешательства

• Препарат BGB-B2033
  Administered by intravenous infusion
• Препарат Tislelizumab
  Administered by intravenous infusion
• Препарат Bevacizumab
  Administered by intravenous infusion

Первичные конечные точки

• Part A and B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Up to approximately 2 years]
• Part A and B: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-B2033 [Срок оценки: Up to approximately 2 years]
• Part A and B: Recommended Phase 2 dose (RP2D) of BGB-B2033 [Срок оценки: Up to approximately 2 years]
• Part C and D: Overall Response Rate (ORR) as assessed by the Independent Review Committee (IRC) [Срок оценки: Up to approximately 2 years]

Вторичные конечные точки (11)

• Part A and B: Overall Response Rate (ORR) as assessed by the investigator [Срок оценки: Up to approximately 2 years]
• Part A and B: Duration of Response (DOR) as assessed by the investigator [Срок оценки: Up to approximately 2 years]
• Part A and B: Disease Control Rate (DCR) as assessed by the investigator [Срок оценки: Up to approximately 2 years]
• Part A and B: Progression Free Survival (PFS) as assessed by the investigator [Срок оценки: Up to approximately 2 years]
• Part A and B: Serum concentration of of BGB-B2033 [Срок оценки: Up to approximately 2 years]
• Part A and B: Number of participants with anti-drug antibodies (ADAs) to BGB-B2033 [Срок оценки: Up to approximately 2 years]
• Part C and D: Overall Response Rate (ORR) as assessed by the investigator [Срок оценки: Up to approximately 2 years]
• Part C and D: Duration of Response (DOR) as assessed by the investigator and IRC [Срок оценки: Up to approximately 2 years]
• Part C and D: Progression Free Survival (PFS) as assessed by the investigator and IRC [Срок оценки: Up to approximately 2 years]
• Part C and D: Overall Survival (OS) [Срок оценки: Up to approximately 2 years]
• Part C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Up to approximately 2 years]

Критерии участия

Критерии включения

• Participants must have one of the following unresectable, locally advanced, or metastatic tumor types:

• Hepatocellular carcinoma (HCC): Histologically or cytologically confirmed HCC that is either Barcelona Clinic Liver Cancer (BCLC) Stage C, or BCLC Stage B that is not amenable to, or has progressed after, loco-regional therapy and is not eligible for a curative treatment approach.
• Alpha-fetoprotein (AFP)-producing gastric cancer (GC): Histologically confirmed GC with AFP > 20 ng/mL in blood or tumor tissue positive for AFP by a validated immunohistochemistry (IHC) assay based on local or central testing.
• Germ cell tumors: Histologically confirmed germ cell tumors including extragonadal yolk sac tumors (e.g., located in the mediastinum, vagina, brain, retroperitoneum), and non-dysgerminomas for which no further curative systemic treatment options exist.
• Glypican-3 (GPC3)-positive squamous non-small cell lung cancer (NSCLC): Histologically confirmed GPC3-positive squamous NSCLC with prior exposure to a checkpoint inhibitor (CPI).
• At least one evaluable lesion for dose escalation, and
• At least one measurable lesion for safety expansion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Adequate organ function as defined in the protocol.
• Provision of tumor tissue samples is required for specified parts of the study.

Критерии исключения

• Prior therapy directed against glypican-3 (GPC3) or the T-cell costimulatory receptor 4-1BB (CD137).
• Active leptomeningeal disease or uncontrolled/untreated brain metastases.
• Active autoimmune disease or a history of autoimmune disease with potential for relapse.
• Any malignancy diagnosed ≤ 2 years before the first dose of study drug(s), except: The cancer type under investigation in this study, or Locally recurring malignancies previously treated with curative intent.
• Requirement for systemic corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive therapy within 14 days prior to the first dose of study drug(s).
• Certain comorbidities involving the lungs, heart, bleeding conditions, or active infections, as defined in the protocol.

Note: Additional protocol-defined inclusion and 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

Китай · 18 центров

• Anhui Provincial Hospital — Хэфэй
• Chongqing University Cancer Hospital — Чунцин
• Mengchao Hepatobiliary Hospital of Fujian Medical University — Фучжоу
• Zhujiang Hospital of Southern Medical University — Гуанчжоу
• Nanfang Hospital of Southern Medical University — Гуанчжоу
• Guangxi Medical University Cancer Hospital Wuxiang Branch — Nanning
• The Fourth Hospital of Hebei Medical University — Shijiazhuang
• Harbin Medical University Cancer Hospital — Харбин
• … и ещё 10 центров

США · 7 центров

• City of Hope Phoenix Cancer Center — Goodyear
• City of Hope National Medical Center — Duarte
• City of Hope Chicago Cancer Center — Zion
• Memorial Sloan Kettering Cancer Center Mskcc — New York
• Upmc Hillman Cancer Center(Univ of Pittsburgh) — Pittsburgh
• Scri Oncology Partners — Nashville
• The University of Texas Md Anderson Cancer Center — Houston

South Korea · 7 центров

• Chungbuk National University Hospital — Cheongju-si
• Cha Bundang Medical Center, Cha University — BundangGu SeongnamSi
• Seoul National University Bundang Hospital — Seongnam-si
• Samsung Medical Center — GangnamGu
• Severance Hospital Yonsei University Health System — SeodaemunGu
• Seoul National University Hospital — Seoul
• Asan Medical Center — SongpaGu

Бразилия · 4 центра

• Centro Gaucho Integrado de Oncologia Hospital Mae de Deus — Porto Alegre
• Hospital Da Bahia — Salvador
• Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto — São José do Rio Preto
• Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira — São Paulo

Италия · 4 центра

• Irccs Istituto Nazionale Tumori Fondazione Pascale — Naples
• Iov Istituto Oncologico Veneto Irccs — Padova
• Fondazione Policlinico Universitario Agostino Gemelli — Roma
• Irccs Humanitas Research Hospital — Rozzano

Франция · 3 центра

• Hopital Beaujon — Clichy
• Centre Hospitalier Universitaire Nantes Hotel Dieu — Nantes
• Institut Gustave Roussy — Villejuif

Япония · 3 центра

• Kindai University Hospital — Sakai
• Tokyo Metropolitan Komagome Hospital — Bunkyoku
• Cancer Institute Hospital of Jfcr — Kotoku

Новая Зеландия · 1 центр

• Auckland City Hospital — Auckland

Пуэрто-Рико · 1 центр

• Hospital Oncologico — Rio Piedras

Идентификаторы

NCT: NCT06427941 · BGB-B2033-101 · 2025-524136-19-00 · jRCT2051260010 · BGB-B2033-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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