A Study of ZW251 in Participants With Advanced Solid Tumors

May 5, 2026 updated by: Zymeworks BC Inc.

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Ireland
      • Dublin, Ireland, D07 R2WY
        • Recruiting
        • START - Dublin Mater Misericordiae University Hospital (MMUH)
        • Principal Investigator:
          • Austin Duffy, MD, DMed
  • Japan
      • Kashiwa, Japan, 2778577
        • Recruiting
        • National Cancer Center East
        • Principal Investigator:
          • Masafumi Ikeda, MD, PhD
      • Kyoto, Japan, 606-8507
        • Recruiting
        • Kyoto University Hospital
        • Principal Investigator:
          • Takako Nakajima, MD
      • Osaka, Japan, 573-1191
        • Recruiting
        • Kansai Medical University Hospital
        • Principal Investigator:
          • Toshio Shimizu, MD, PhD
      • Tokyo, Japan, 104-0045
        • Recruiting
        • National Cancer Center Hospital
        • Principal Investigator:
          • Yuta Maruki, MD
  • Portugal
      • Lisbon, Portugal, 1649-035
        • Recruiting
        • START Lisboa a - Unidade de Ensaios ClÃnicos - Hospital de Santa Maria
        • Principal Investigator:
          • Andre Mansinho, MD, MSc
      • Vila Nova de Gaia, Portugal, 4434-502
        • Recruiting
        • Unidade Local de Saude Gaia E Espinho
        • Principal Investigator:
          • Andreia Capela, MD
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitario Vall d'Hebron
        • Principal Investigator:
          • Jaume Capdevila Castillon, MD, PhD
      • Barcelona, Spain, 29010
        • Recruiting
        • START Barcelona
        • Principal Investigator:
          • Tatiana Hernandez Guerrero, MD, PhD
      • Logroño, Spain, 26006
        • Recruiting
        • START - Rioja Hospital Universitario San Pedro
        • Principal Investigator:
          • Maria Jose de Miguel Luken, MD
      • Madrid, Spain, 28223
        • Recruiting
        • NEXT Oncology Madrid
        • Principal Investigator:
          • Valentina Boni, MD, PhD
      • Madrid, Spain, 28050
        • Recruiting
        • START Madrid Hospital Universitario HM Sanchinarro - CIOCC
        • Principal Investigator:
          • Emiliano Calvo, MD, PhD
      • Madrid, Spain, 28040
        • Recruiting
        • START Madrid Hospital Universitario Fundacion Jimenez Diaz
        • Principal Investigator:
          • Manuel Pedregal Trujillo, MD
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Universitario Virgen de la Victoria
        • Principal Investigator:
          • Javier Garcia Corbacho, MD
      • Pamplona, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
        • Principal Investigator:
          • Bruno Sangro, MD, PhD
  • Taiwan
      • Taipei, Taiwan, 100225
        • Recruiting
        • National Taiwan University Hospital
        • Principal Investigator:
          • Ann Lii Cheng, MD
      • Taipei, Taiwan, 112201
        • Recruiting
        • Taipei Veterans General Hospital
        • Principal Investigator:
          • Yi-Hsiang Huang, MD, PhD
  • United States
    • California
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Comprehensive Cancer Center
        • Principal Investigator:
          • Katie Kelley, MD
      • Santa Monica, California, United States, 90404
        • Recruiting
        • University of California Los Angeles - Cancer Care - Santa Monica (UCLA)
        • Principal Investigator:
          • Richard Finn, MD
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Cancer Institute
        • Principal Investigator:
          • John Hamm, MD FACP, FASCO
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • START MidWest
        • Principal Investigator:
          • Sreenivasa Chandana, MD, PhD
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Principal Investigator:
          • Martin Gutierrez, MD
    • New York
      • New York, New York, United States, 10065-6800
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Ghassan Abou-Alfa, MD, JD, MBA, PhD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Ecaterina Dumbrava, MD
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • START San Antonio
        • Principal Investigator:
          • Muralidhar Beeram, MD, MBBS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ZW251
Drug: ZW251
Administered intravenously

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Up to 3 weeks
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
Up to approximately 2 years
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
Up to approximately 2 years
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
Up to approximately 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)
Time Frame: Up to approximately 2 years
Number of participants who develop ADAs
Up to approximately 2 years
Best overall response (Parts 1 and 2)
Time Frame: Up to approximately 2 years
Up to approximately 2 years
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
Up to approximately 2 years
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
Up to approximately 2 years
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
Up to approximately 2 years
Maximum concentration (Cmax) of ZW251 (Parts 1 and 2)
Time Frame: Up to approximately 2 years
ZW251 maximum concentration after first dose administration
Up to approximately 2 years
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
Up to approximately 2 years
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
Up to approximately 2 years
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
Up to approximately 2 years
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
Up to approximately 2 years
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
Up to approximately 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zymeworks BC Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Maggie Weinstein, MD, PhD, MPH, Zymeworks BC Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 21, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 27, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 5, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 7, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZWI-ZW251-101
  • 2025-523088-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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