A Study of ZW251 in Participants With Advanced Solid Tumors

Not Applicable

Recruiting

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: ZW251

• Registration Number: NCT07164313
• Lead Sponsor: Zymeworks BC Inc.

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).

Detailed Description

Part 1 (dose escalation) of the study will evaluate the safety and tolerability of ZW251 in HCC. 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 Timeline

• Study First Submitted: 2025-08-27
• Status Verified: 2025-09
• Study Start: 2025-09-01
• Study First Submitted QC: 2025-09-05
• Study First Posted: 2025-09-10
• Last Update Submitted: 2025-09-17
• Last Update Posted: 2025-09-18
• Primary Completion: 2027-09
• Study Completion: 2028-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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
• 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
• 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
• Portal vein thrombosis within 3 months prior to Cycle 1 Day 1 that require coagulation therapy or is not stable
• Known gastrointestinal bleeding within 3 months
• Acute or chronic uncontrolled renal disease, pancreatitis, or non-malignant liver disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ZW251	ZW251	-

Primary Outcome Measures

Name	Time	Method
Incidence of dose-limiting toxicities (DLTs; Part 1)	Up to 3 weeks	Number of participants who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to ZW251
Incidence of AEs (Parts 1 and 2)	Up to approximately 2 years	Number of participants who experienced AEs, adverse events of special interest, or serious adverse events
Incidence of clinical laboratory abnormalities (Parts 1 and 2)	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
Confirmed objective response rate (Part 2)	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

Secondary Outcome Measures

Name	Time	Method
Area under the concentration-time curve of ZW251 at steady state (AUCtau,ss; Parts 1 and 2)	Up to approximately 2 years	Area under the concentration-time curve of ZW251 at steady state after fourth dose administration
Confirmed objective response rate (Part 1)	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
Best overall response (Parts 1 and 2)	Up to approximately 2 years
Disease control rate (Parts 1 and 2)	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
Duration of response (Parts 1 and 2)	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
Progression-free survival (Parts 1 and 2)	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
Overall survival (Part 2)	Up to approximately 2 years	The time from the date of the first dose of study treatment to the date of death due to any cause
Area under the concentration-time curve (AUC0-504) of ZW251 (Parts 1 and 2)	Up to approximately 2 years	Area under the concentration-time curve of ZW251 after first dose administration
Maximum concentration (Cmax) of ZW251 (Parts 1 and 2)	Up to approximately 2 years	ZW251 maximum concentration after first dose administration
Maximum concentration of ZW251 at steady state (Сmax,ss; Parts 1 and 2)	Up to approximately 2 years	ZW251 maximum concentration at steady state after fourth dose administration
Minimal concentration of ZW251 at steady state (Сmin,ss; Parts 1 and 2)	Up to approximately 2 years	ZW251 minimal concentration at steady state after fourth dose administration
Incidence of anti-drug antibodies (ADAs; Parts 1 and 2)	Up to approximately 2 years	Number of participants who develop ADAs

Trial Locations

Locations (1)

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States