NCT07164313

Brief 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).

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P75+ for phase_1 hepatocellular-carcinoma

Timeline
24mo left

Started Oct 2025

Geographic Reach
6 countries

23 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress22%
Oct 2025May 2028

First Submitted

Initial submission to the registry

August 27, 2025

Completed
14 days until next milestone

First Posted

Study publicly available on registry

September 10, 2025

Completed
1 month until next milestone

Study Start

First participant enrolled

October 21, 2025

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2027

Expected
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2028

Last Updated

April 14, 2026

Status Verified

April 1, 2026

Enrollment Period

1.9 years

First QC Date

August 27, 2025

Last Update Submit

April 8, 2026

Conditions

Hepatocellular CarcinomaGerm Cell TumorSquamous Cell Non-Small Cell Lung Cancer

Keywords

GPC3-expressing cancerhepatocellular carcinomaantibody drug conjugateADCLung CancerNon-Small Cell Lung CancerSquamous Cell CancerGerm Cell Tumor

Outcome Measures

Primary Outcomes (4)

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

    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)

    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)

    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)

    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 Outcomes (11)

  • Objective response rate (Part 1)

    Up to approximately 2 years

  • Best overall response (Parts 1 and 2)

    Up to approximately 2 years

  • Disease control rate (Parts 1 and 2)

    Up to approximately 2 years

  • Duration of response (Parts 1 and 2)

    Up to approximately 2 years

  • Progression-free survival (Part 2)

    Up to approximately 2 years

  • +6 more secondary outcomes

Study Arms (1)

ZW251

EXPERIMENTAL
Drug: ZW251

Interventions

ZW251DRUG

Administered intravenously

ZW251

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (23)

UCSF Comprehensive Cancer Center

San Francisco, California, 94158, United States

RECRUITING

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

Santa Monica, California, 90404, United States

RECRUITING

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

RECRUITING

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

START - Dublin Mater Misericordiae University Hospital (MMUH)

Dublin, D07 R2WY, Ireland

RECRUITING

National Cancer Center East

Kashiwa, 2778577, Japan

RECRUITING

Kyoto University Hospital

Kyoto, 606-8507, Japan

RECRUITING

Kansai Medical University Hospital

Osaka, 573-1191, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, 104-0045, Japan

RECRUITING

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

Lisbon, 1649-035, Portugal

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

START Barcelona

Barcelona, 29010, Spain

RECRUITING

START - Rioja Hospital Universitario San Pedro

Logroño, 26006, Spain

RECRUITING

START Madrid Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

START Madrid Hospital Universitario HM Sanchinarro - CIOCC

Madrid, 28050, Spain

RECRUITING

NEXT Oncology Madrid

Madrid, 28223, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, 31008, Spain

RECRUITING

National Taiwan University Hospital

Taipei, 100225, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

RECRUITING

MeSH Terms

Conditions

Carcinoma, HepatocellularNeoplasms, Germ Cell and EmbryonalLung NeoplasmsCarcinoma, Non-Small-Cell LungNeoplasms, Squamous Cell

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver DiseasesRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinoma, BronchogenicBronchial Neoplasms

Study Officials

  • Maggie Weinstein, MD, PhD, MPH

    Zymeworks BC Inc.

    STUDY DIRECTOR

Central Study Contacts

Zymeworks Clinical Trial Resource

CONTACT

(206) 237-1030medinfo@zymeworks.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 27, 2025

First Posted

September 10, 2025

Study Start

October 21, 2025

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

May 1, 2028

Last Updated

April 14, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

PT(1)ES(8)IE(1)US(7)JP(4)TW(2)