GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma

Inclusion Criteria:

1. Subjects must have confirmed diagnosis of aHCC (locally advanced or metastatic hepatocellular carcinoma) by radiography, histology and/or cytology, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and/or locoregional therapies (fibrolamellar, sarcomatoid HCC and mixed hepatocellular / cholangiocarcinoma subtypes are not eligible);
2. Have Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy;
3. Have documented disease progression after or intolerance to first line treatment of immune checkpoint inhibitors(ICI)
4. Child-Pugh score ≤ 6 (Child-Pugh A) score within 7 days of first dose of study drug;
5. ECOG performance status: 0-1 within 7 days of first dose of study drug;
6. Have a predicted life expectancy of greater than 3 months;
7. Adequate hematologic and end-organ function functions of the important organs are confirmed.

Exclusion Criteria:

1. Presence of tumor thrombus involving main trunk of portal vein (Vp4), inferior vena cava, cardiac involvement of HCC;
2. Subjects with untreated or incompletely treated varices with bleeding or high-risk for bleeding. Has had esophageal or gastric variceal bleeding within the last 6 months;
3. History of encephalopathy;
4. Has a known history of, or any evidence of central nervous system (CNS) metastases and/or carcinomatous meningitis;
5. Had history of a solid organ or hematologic transplant;
6. Has received locoregional therapy to liver (TACE, TAE, hepatic arterial infusion [HAI], radiation, radioembolization or ablation) within 4 weeks of start of study treatment.
7. Had prior systemic TKI treatment prior to start of study treatment;
8. Has received prior immune checkpoint inhibitors within 4 weeks of start of study treatment;
9. Has received Nivolumab in the first-line systemic therapy:

Active co-infection with:

1. Both hepatitis B and C as evidenced by positive HBV surface antigen or detectable HBV DNA and HCV RNA, OR
2. Hepatitis D infection in subjects with hepatitis B
3. Has an active bacterial or fungal infection requiring systemic therapy within 7 days prior to study drug dosing;
4. Has a known history of active tuberculosis (Bacillus Tuberculosis);
5. Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture;
6. Thrombotic or embolic events (except HCC tumor thrombus) within the past 6 months, such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism; If prior history of deep vein thrombosis (DVT) / (pulmonary embolism (PE), the subject needs to be on stable doses of anticoagulation with low molecular weight heparin or oral anticoagulant for at least two weeks;
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
8. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis;
9. Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial;