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ZW251 for advanced liver, lung, and germ cell cancers

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

Phase 1 Interventional Zymeworks BC Inc. · NCT07164313

This will test whether ZW251, an antibody-drug conjugate that targets GPC3, is safe and can shrink tumors in adults with advanced hepatocellular carcinoma, squamous cell non-small cell lung cancer, or germ cell tumors.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment100 (estimated)
Ages18 Years and up
SexAll
SponsorZymeworks BC Inc. Industry-sponsored
Locations25 sites (San Francisco, California and 24 other locations)
Trial IDNCT07164313 on ClinicalTrials.gov

What this trial studies

This Phase 1, multi-center study enrolls adults with advanced HCC, squamous cell NSCLC, or yolk sac/choriocarcinoma-predominant germ cell tumors to receive ZW251, an antibody-drug conjugate targeting glypican-3 (GPC3). Part 1 uses a dose-escalation design to define safety, tolerability, and a recommended dose, and Part 2 expands at the selected dose to further monitor safety and preliminary anti-tumor activity in HCC. Eligible participants must have measurable disease by RECIST v1.1, ECOG performance status 0–1, and adequate organ function, with HCC patients limited to Child-Pugh class A. Study visits and treatment are provided at participating academic and regional cancer centers in the United States.

Who should consider this trial

Good fit: Adults with unresectable or metastatic HCC, squamous cell NSCLC, or yolk sac/choriocarcinoma-predominant germ cell tumors who have measurable disease, ECOG 0–1, and adequate organ function (HCC patients Child-Pugh A) are the intended candidates.

Not a fit: Patients with poor performance status (ECOG >1), compromised liver function (Child-Pugh B/C for HCC), recent active treatment for another progressing malignancy, or tumors that do not express GPC3 may be less likely to benefit.

Why it matters

Potential benefit: If successful, ZW251 could provide a new targeted treatment option for patients with GPC3-expressing tumors, potentially shrinking tumors or controlling disease when other therapies have failed.

How similar studies have performed: Antibody-drug conjugates have shown meaningful clinical activity in other tumor types, but GPC3-targeted ADCs are a relatively new approach with limited published clinical results to date.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

San Francisco, California and 24 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Hepatocellular CarcinomaSquamous Cell Non-Small Cell Lung CancerGerm Cell TumorGPC3-expressing cancerhepatocellular carcinomaantibody drug conjugateADCLung Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.