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NCT07164313PHASE1Recruiting

A Study of ZW251 in Participants With Advanced Solid Tumors

Zymeworks BC Inc.

Start Date

10/21/2025

Completion Date

5/1/2028

Summary

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).

Detailed Description

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Interventions

DRUG

ZW251

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Conditions

Hepatocellular CarcinomaSquamous Cell Non-Small Cell Lung CancerGerm Cell Tumor

Locations

UCSF Comprehensive Cancer Center

San Francisco, California 94158

United States

University of California Los Angeles - Cancer Care - Santa Monica (UCLA)

Santa Monica, California 90404

United States

Norton Cancer Institute

Louisville, Kentucky 40202

United States

START Midwest

Grand Rapids, Michigan 49546

United States

Hackensack University Medical Center

Hackensack, New Jersey 07601

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065-6800

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

START San Antonio

San Antonio, Texas 78229

United States

START - Dublin Mater Misericordiae University Hospital (MMUH)

Dublin, D07 R2WY

Ireland

National Cancer Center East

Kashiwa, 2778577

Japan

Kyoto University Hospital

Kyoto, 606-8507

Japan

Kansai Medical University Hospital

Osaka, 573-1191

Japan

National Cancer Center Hospital

Tokyo, 104-0045

Japan

START Lisboa a - Unidade de Ensaios ClÃnicos - Hospital de Santa Maria

Lisbon, 1649-035

Portugal

Unidade Local de Saúde Gaia e Espinho

Vila Nova de Gaia, 4434-502

Portugal

Hospital Universitario Vall d'Hebron

Barcelona, 08035

Spain

START Barcelona

Barcelona, 29010

Spain

START - Rioja Hospital Universitario San Pedro

Logroño, 26006

Spain

START Madrid Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040

Spain

START Madrid Hospital Universitario HM Sanchinarro - CIOCC

Madrid, 28050

Spain

NEXT Oncology Madrid

Madrid, 28223

Spain

Hospital Universitario Virgen de la Victoria

Málaga, 29010

Spain

Clinica Universidad de Navarra

Pamplona, 31008

Spain

National Taiwan University Hospital

Taipei, 100225

Taiwan

Taipei Veterans General Hospital

Taipei, 112201

Taiwan