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).

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.

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