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NCT Number: NCT07164313

A Study of ZW251 in Participants With Advanced Solid Tumors

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).

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Key information

Conditions

Hepatocellular Carcinoma Adenocarcinoma Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Hepatocellular Carcinoma, Non-Small-Cell Lung Digestive System Diseases Digestive System Neoplasms Germ Cell Tumor Liver Diseases Liver Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Squamous Cell Respiratory Tract Diseases Respiratory Tract Neoplasms Squamous Cell Non-small Cell Lung Cancer Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

START - Dublin Mater Misericordiae University Hospital (MMUH), Dublin, Ireland

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ZW251

Drug

Administered intravenously

Primary outcomes

  1. Incidence of dose-limiting toxicities (DLTs; Part 1)

    Time frame: Up to 3 weeks

    Number of participants who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to ZW251

  2. Incidence of AEs (Parts 1 and 2)

    Time frame: Up to approximately 2 years

    Number of participants who experienced AEs, adverse events of special interest, or serious adverse events

  3. Incidence of clinical laboratory abnormalities (Parts 1 and 2)

    Time frame: Up to approximately 2 years

    Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0

  4. Objective response rate (Part 2)

    Time frame: Up to approximately 2 years

    Number of participants who achieved a best overall response of either confirmed complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Secondary outcomes

  1. Objective response rate (Part 1)

    Time frame: Up to approximately 2 years

    Number of participants who achieved a best overall response of either confirmed CR or PR during treatment according to RECIST v1.1

  2. Best overall response (Parts 1 and 2)

    Time frame: Up to approximately 2 years

  3. Disease control rate (Parts 1 and 2)

    Time frame: Up to approximately 2 years

    Number of participants who achieved a best response of CR, PR, or stable disease during treatment per RECIST v1.1

  4. Duration of response (Parts 1 and 2)

    Time frame: Up to approximately 2 years

    The time from the first objective response (CR or PR) to the first documented progressive disease (PD) per RECIST v1.1 or death within 30 days of last dose of study treatment from any cause. Only participants who achieve a confirmed response will be included in the analysis

  5. Progression-free survival (Part 2)

    Time frame: Up to approximately 2 years

    The time from the first dose of study treatment to the date of first documented PD per RECIST v1.1 or death from any cause

  6. Area under the concentration-time curve (AUC0-504) of ZW251 (Parts 1 and 2)

    Time frame: Up to approximately 2 years

    Area under the concentration-time curve of ZW251 after first dose administration

  7. Maximum concentration (Cmax) of ZW251 (Parts 1 and 2)

    Time frame: Up to approximately 2 years

    ZW251 maximum concentration after first dose administration

  8. Area under the concentration-time curve of ZW251 at steady state (AUCtau,ss; Parts 1 and 2)

    Time frame: Up to approximately 2 years

    Area under the concentration-time curve of ZW251 at steady state after fourth dose administration

  9. Maximum concentration of ZW251 at steady state (Сmax,ss; Parts 1 and 2)

    Time frame: Up to approximately 2 years

    ZW251 maximum concentration at steady state after fourth dose administration

  10. Minimal concentration of ZW251 at steady state (Сmin,ss; Parts 1 and 2)

    Time frame: Up to approximately 2 years

    ZW251 minimal concentration at steady state after fourth dose administration

  11. Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)

    Time frame: Up to approximately 2 years

    Number of participants who develop ADAs

Study contacts

Contact information is provided by the study sponsor or research team.

Zymeworks Clinical Trial Resource

CONTACT

[email protected]

(206) 237-1030

Sponsors and collaborators

Lead sponsor

Zymeworks BC Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Sep 10, 2025
Registry last updated
May 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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