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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

100

Phase

  • 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 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

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
Intervention / Treatment
Experimental: ZW251
Drug: ZW251
Administered intravenously

What is the study measuring?

Primary Outcome Measures

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

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

Zymeworks BC Inc.

Investigators

  • 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)

October 21, 2025

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

August 27, 2025

First Submitted That Met QC Criteria

September 5, 2025

First Posted (Actual)

September 10, 2025

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

May 5, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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