Hepatocellular CarcinomaPhase 1NCT07164313
A Study of ZW251 in Participants With Advanced Solid Tumors
A Phase 1 study testing ZW251 in people with Hepatocellular Carcinoma and Squamous Cell Non-Small Cell Lung Cancer, run by Zymeworks BC Inc. at 25 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Squamous Cell Non-Small Cell Lung Cancer, Germ Cell Tumor
- What is being tested?
- ZW251
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 25 sitesin 6 countries
- Study dates
- 21 Oct 2025to May 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
25 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
25 sites in 6 countries
United States8 sites, 8 recruiting
- Recruiting
START Midwest
Grand Rapids, Michigan, 49546
Sreenivasa Chandana, MD, PhD
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Martin Gutierrez, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Ecaterina Dumbrava, MD
- Recruiting
Norton Cancer Institute
Louisville, Kentucky, 40202
John Hamm, MD FACP, FASCO
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065-6800
Ghassan Abou-Alfa, MD, JD, MBA, PhD
- Recruiting
START San Antonio
San Antonio, Texas, 78229
Muralidhar Beeram, MD, MBBS
- Recruiting
UCSF Comprehensive Cancer Center
San Francisco, California, 94158
Katie Kelley, MD
- Recruiting
University of California Los Angeles - Cancer Care - Santa Monica (UCLA)
Santa Monica, California, 90404
Richard Finn, MD
Spain8 sites, 8 recruiting
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Jaume Capdevila Castillon, MD, PhD
- Recruiting
START Barcelona
Barcelona, 29010
Tatiana Hernandez Guerrero, MD, PhD
- Recruiting
START - Rioja Hospital Universitario San Pedro
Logroño, 26006
Maria Jose de Miguel Luken, MD
- Recruiting
START Madrid Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Manuel Pedregal Trujillo, MD
- Recruiting
START Madrid Hospital Universitario HM Sanchinarro - CIOCC
Madrid, 28050
Emiliano Calvo, MD, PhD
- Recruiting
NEXT Oncology Madrid
Madrid, 28223
Valentina Boni, MD, PhD
- Recruiting
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Javier Garcia Corbacho, MD
- Recruiting
Clinica Universidad de Navarra
Pamplona, 31008
Bruno Sangro, MD, PhD
Japan4 sites, 4 recruiting
- Recruiting
National Cancer Center East
Kashiwa, 2778577
Masafumi Ikeda, MD, PhD
- Recruiting
Kyoto University Hospital
Kyoto, 606-8507
Takako Nakajima, MD
- Recruiting
Kansai Medical University Hospital
Osaka, 573-1191
Toshio Shimizu, MD, PhD
- Recruiting
National Cancer Center Hospital
Tokyo, 104-0045
Yuta Maruki, MD
Portugal2 sites, 2 recruiting
- Recruiting
START Lisboa a - Unidade de Ensaios ClÃnicos - Hospital de Santa Maria
Lisbon, 1649-035
Andre Mansinho, MD, MSc
- Recruiting
Unidade Local de Saúde Gaia e Espinho
Vila Nova de Gaia, 4434-502
Andreia Capela, MD
Taiwan2 sites, 2 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, 100225
Ann Lii Cheng, MD
- Recruiting
Taipei Veterans General Hospital
Taipei, 112201
Yi-Hsiang Huang, MD, PhD
Ireland1 site, 1 recruiting
- Recruiting
START - Dublin Mater Misericordiae University Hospital (MMUH)
Dublin, D07 R2WY
Austin Duffy, MD, DMed
About this study
Official 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
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).
Read the 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.
- Being tested
- ZW251
- Keywords
- GPC3-expressing cancer, hepatocellular carcinoma, antibody drug conjugate, ADC, Lung Cancer, Non-Small Cell Lung Cancer, Squamous Cell Cancer, Germ Cell Tumor
- Medical subject headings
- Carcinoma, Hepatocellular, Neoplasms, Germ Cell and Embryonal, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Neoplasms, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZW251Drug
Administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| ZW251 | Experimental | Not described Receives: Drug: ZW251 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to approximately 2 years
Secondary outcomes (11)
Objective response rate (Part 1)
Number of participants who achieved a best overall response of either confirmed CR or PR during treatment according to RECIST v1.1
Measured: Up to approximately 2 years
Best overall response (Parts 1 and 2)
Measured: Up to approximately 2 years
Disease control rate (Parts 1 and 2)
Number of participants who achieved a best response of CR, PR, or stable disease during treatment per RECIST v1.1
Measured: Up to approximately 2 years
Duration of response (Parts 1 and 2)
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
Measured: Up to approximately 2 years
Progression-free survival (Part 2)
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
Measured: Up to approximately 2 years
Area under the concentration-time curve (AUC0-504) of ZW251 (Parts 1 and 2)
Area under the concentration-time curve of ZW251 after first dose administration
Measured: Up to approximately 2 years
Maximum concentration (Cmax) of ZW251 (Parts 1 and 2)
ZW251 maximum concentration after first dose administration
Measured: Up to approximately 2 years
Area under the concentration-time curve of ZW251 at steady state (AUCtau,ss; Parts 1 and 2)
Area under the concentration-time curve of ZW251 at steady state after fourth dose administration
Measured: Up to approximately 2 years
Maximum concentration of ZW251 at steady state (Сmax,ss; Parts 1 and 2)
ZW251 maximum concentration at steady state after fourth dose administration
Measured: Up to approximately 2 years
Minimal concentration of ZW251 at steady state (Сmin,ss; Parts 1 and 2)
ZW251 minimal concentration at steady state after fourth dose administration
Measured: Up to approximately 2 years
Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)
Number of participants who develop ADAs
Measured: Up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2025
- Study start21 Oct 2025
- Primary completionSep 2027 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zymeworks BC Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Maggie Weinstein, MD, PhD, MPH, Study director, Zymeworks BC Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07164313
- Sponsor's protocol ID
- ZWI-ZW251-101
- Other IDs
- 2025-523088-39, 2025
- Status last verified
- Oct 2026
- First submitted
- 27 Aug 2025
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No