A Study of ZW251 in Participants With Advanced Solid Tumors

Официальное название

A First-In-Human, Phase 1, Open-Label, Multicenter Study of ZW251, a Novel Glypican-3 Targeting Antibody-Drug Conjugate, in Participants With Advanced Solid Tumors, Including Hepatocellular Carcinoma

Обзор

The purpose of this study is to find out if ZW251, an antibody-drug conjugate targeting glypican-3 (GPC3), is safe and can treat participants with advanced cancers, including hepatocellular carcinoma (HCC), squamous cell non-small cell lung cancer (NSCLC), or germ cell tumors (GCT).

Подробное описание

Part 1 (dose escalation) of the study will evaluate the safety and tolerability of ZW251 in HCC, squamous cell NSCLC, and GCT. Part 2 (dose optimization) of the study will further assess safety and potential anti-tumor activity of the ZW251 established recommended doses in HCC.

Вмешательства

• Препарат ZW251
  Administered intravenously

Первичные конечные точки

• Incidence of dose-limiting toxicities (DLTs; Part 1) [Срок оценки: Up to 3 weeks]
• Incidence of AEs (Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Incidence of clinical laboratory abnormalities (Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Objective response rate (Part 2) [Срок оценки: Up to approximately 2 years]

Вторичные конечные точки (11)

• Objective response rate (Part 1) [Срок оценки: Up to approximately 2 years]
• Best overall response (Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Disease control rate (Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Duration of response (Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Progression-free survival (Part 2) [Срок оценки: Up to approximately 2 years]
• Area under the concentration-time curve (AUC0-504) of ZW251 (Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Maximum concentration (Cmax) of ZW251 (Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Area under the concentration-time curve of ZW251 at steady state (AUCtau,ss; Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Maximum concentration of ZW251 at steady state (Сmax,ss; Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Minimal concentration of ZW251 at steady state (Сmin,ss; Parts 1 and 2) [Срок оценки: Up to approximately 2 years]
• Incidence of anti-drug antibodies (ADAs; Parts 1 and 2) [Срок оценки: Up to approximately 2 years]

Критерии участия

Критерии включения

• Pathologically or cytologically confirmed diagnosis of HCC with evidence of locally advanced (unresectable, and ineligible for transplant) and/or metastatic disease. Noninvasive methods may be used to confirm diagnosis
• Pathologically or cytologically confirmed diagnosis of squamous cell NSCLC with evidence of locally advanced (unresectable) and/or metastatic disease
• Pathologically or cytologically confirmed diagnosis of GCT with evidence of yolk sac and/or choriocarcinoma predominant component and locally advanced (unresectable) and/or metastatic disease
• Measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Liver function status of Child-Pugh Class A (for HCC only)
• Adequate organ function

Критерии исключения

• Known additional malignancy that is progressing or that has required active treatment within the last year
• History of hepatic encephalopathy within the past 6 months or requirement for medications to control encephalopathy
• Participants with HCC experiencing main portal vein tumor invasion require sponsor approval for enrollment
• Known gastrointestinal bleeding within 3 months
• Acute or chronic uncontrolled renal disease, pancreatitis, or non-malignant liver disease

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• UCSF Comprehensive Cancer Center — San Francisco
• University of California Los Angeles - Cancer Care - Santa Monica (UCLA) — Santa Monica
• Norton Cancer Institute — Louisville
• START Midwest — Grand Rapids
• Hackensack University Medical Center — Hackensack
• Memorial Sloan Kettering Cancer Center — New York
• MD Anderson Cancer Center — Houston
• START San Antonio — San Antonio

Испания · 8 центров

• Hospital Universitario Vall d'Hebron — Barcelona
• START Barcelona — Barcelona
• START - Rioja Hospital Universitario San Pedro — Logroño
• START Madrid Hospital Universitario Fundacion Jimenez Diaz — Madrid
• START Madrid Hospital Universitario HM Sanchinarro - CIOCC — Madrid
• NEXT Oncology Madrid — Madrid
• Hospital Universitario Virgen de la Victoria — Málaga
• Clinica Universidad de Navarra — Pamplona

Япония · 4 центра

• National Cancer Center East — Kashiwa
• Kyoto University Hospital — Kyoto
• Kansai Medical University Hospital — Osaka
• National Cancer Center Hospital — Tokyo

Португалия · 2 центра

• START Lisboa a - Unidade de Ensaios ClÃnicos - Hospital de Santa Maria — Lisbon
• Unidade Local de Saúde Gaia e Espinho — Vila Nova de Gaia

Тайвань · 2 центра

• National Taiwan University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei

Ирландия · 1 центр

• START - Dublin Mater Misericordiae University Hospital (MMUH) — Dublin

Идентификаторы

NCT: NCT07164313 · ZWI-ZW251-101 · 2025-523088-39

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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