A Phase I Study of GC33 in Advanced or Metastatic Liver Cancer (Hepatocellular Carcinoma)

This is a Phase I open-label dose escalation study of GC33 in patients with advanced or metastatic HCC. This study is designed to evaluate safety, tolerability, pharmacokinetics, and preliminary assessment of anti-tumor activity. Enrollment will proceed until a maximum tolerated dose (MTD) and a recommended Phase II dose has been established.

Inclusion criteria

• Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form
• Male or female ≥ 18 years old.
• Life expectancy ≥ 3 months.
• ECOG Performance Status of 0-1.
• Histologically confirmed hepatocellular carcinoma (without fibrolamellar subtype).
• Not a candidate for curative treatments.
• Child-Pugh A or B.
• Hematological, Biochemical and Organ Function:

• AST (SGOT): ≤ 5.0 × ULN
• ALT (SGPT): ≤ 5.0 × ULN
• Total Bilirubin: ≤ 3.0 × ULN
• Platelets: ≥ 50,000/μL
• Absolute Neutrophil Count: ≥ 1,500/μL
• Serum creatinine: ≤ 2.0 × ULN
• PT-INR: ≤ 2.0,
• Ability to provide a tumor tissue sample either by:

• a sample obtained within 3 months prior to informed consent for HCC diagnosis. Resection samples are not acceptable.
• undergo a biopsy to confirm HCC diagnosis
• At least one measurable lesion based on Response Evaluation Criteria In Solid Tumors criteria.

(Extension Phase)

• Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form.
• Male or female ≥ 18 years old.
• Life expectancy ≥ 3 months.
• ECOG Performance Status of 0-1.
• Histologically confirmed hepatocellular carcinoma (without fibrolamellar subtype).
• Not a candidate for curative treatments.
• Child-Pugh A.
• Hematological, Biochemical and Organ Function:

• AST (SGOT): ≤ 5.0 × ULN
• ALT (SGPT): ≤ 5.0 × ULN
• Total Bilirubin: ≤ 3.0 × ULN
• Platelets: ≥ 50,000/μL
• Absolute Neutrophil Count: ≥ 1,500/μL
• Serum creatinine: ≤ 2.0 × ULN
• PT-INR: ≤ 2.0
• IHC confirmed GPC3-positive HCC tumor tissue. Tumor tissue sample may be provided by:

• A formalin fixed paraffin embedded block sample within 12 months prior to informed consent for HCC diagnosis;
• Unstained slides obtained within 3 months prior to informed consent for HCC diagnosis;
• Undergo biopsy to confirm GPC3-positive HCC.
• Resection samples are not acceptable.
• At least one measurable lesion based on Response Evaluation Criteria In Solid Tumors criteria.

Exclusion criteria

• Child-Pugh C.
• Pregnant or lactating women or women of child-bearing potential and men of childbearing potential not willing to use effective means of contraception.
• Patients known to be positive for Human immunodeficiency virus infection.
• Active infectious diseases requiring treatment except for hepatitis B and C.
• Other malignancies within the last 5 years.
• History of transplantation (organ, bone marrow transplantation,peripheral blood stem cell transplantation, etc.).
• Patients with significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug.
• Patients with brain metastases, other central nervous system or other psychiatric disease.
• Patients who received major surgery, local therapy for HCC, chemotherapy, radiotherapy, hormone-therapy, immunotherapy, or another investigational drug within 4 weeks prior to Day 1.
• Patients who received the following treatments within 2 weeks prior to Day1:

• Anticoagulant or thrombolytic agents for therapeutic purposes.
• Systemic anti-viral therapy for hepatitis C/cirrhosis.
• Blood transfusion
• History of hypersensitivity to similar agents.
• Patient is unable to comply with the requirements of the protocol and/or follow-up procedures.

(Extension Phase)

• Child-Pugh B or C.
• Pregnant or lactating women or women of child-bearing potential and men of childbearing potential not willing to use effective means of contraception.
• Patients known to be positive for Human immunodeficiency virus infection.
• Active infectious diseases requiring treatment except for hepatitis B and C.
• Other malignancies within the last 5 years.
• History of transplantation (organ, bone marrow transplantation, Peripheral blood stem cell transplantation, etc.).
• Patients with significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug.
• Patients with brain metastases, other central nervous system or other psychiatric disease.
• Patients who received major surgery, local therapy for HCC, chemotherapy, radiotherapy, hormone-therapy, immunotherapy, or another investigational drug within 4 weeks prior to Day 1.
• Patients who received the following treatments within 2 weeks prior to Day 1:

• Anticoagulations or thrombolytic agents for therapeutic purposes.
• Systemic anti-viral therapy for hepatitis C/cirrhosis.
• Blood transfusion
• History of hypersensitivity to similar agents.
• Patient is unable to comply with the requirements of the protocol and/or follow-up procedures.
• IHC confirmed GPC3-negative HCC tumor tissue.