GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma

This is a global phase II, open label study in the subjects with Advanced Hepatocellular Carcinoma (aHCC) who were intolerant or had progressed after or intolerant to first-line Immune Checkpoint Inhibitors (ICI) such as Atezolizumab plus Bevacizumab, or ICI plus Tyrosine Kinase Inhibitor (TKI).

Based on published and first-hand experience with the safety and tolerability of both GT90001 and Nivolumab, the proposed dose is GT90001 7 mg/kg in combination with Nivolumab 240 mg, infusion every two weeks.

This study will enroll a total of 105 subjects to receive combinational therapy of Nivolumab and GT90001.

• Nivolumab 240 mg will first be administered by intravenous infusion over 30 minutes, then 30 minutes later, give intravenous infusion of GT90001 7.0 mg/kg over 60 min, once every two weeks.


Eligibility Criteria:
Inclusion Criteria:

* 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);
* Have Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy;
* Have documented disease progression after or intolerance to first line treatment of immune checkpoint inhibitors(ICI)
* Child-Pugh score ≤ 6 (Child-Pugh A) score within 7 days of first dose of study drug;
* ECOG performance status: 0-1 within 7 days of first dose of study drug;
* Have a predicted life expectancy of greater than 3 months;
* Adequate hematologic and end-organ function functions of the important organs are confirmed.

Exclusion Criteria:

* Presence of tumor thrombus involving main trunk of portal vein (Vp4), inferior vena cava, cardiac involvement of HCC;
* 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;
* History of encephalopathy;
* Has a known history of, or any evidence of central nervous system (CNS) metastases and/or carcinomatous meningitis;
* Had history of a solid organ or hematologic transplant;
* Has received locoregional therapy to liver (TACE, TAE, hepatic arterial infusion \[HAI\], radiation, radioembolization or ablation) within 4 weeks of start of study treatment.
* Had prior systemic TKI treatment prior to start of study treatment;
* Has received prior immune checkpoint inhibitors within 4 weeks of start of study treatment;
* 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
* Has an active bacterial or fungal infection requiring systemic therapy within 7 days prior to study drug dosing;
* Has a known history of active tuberculosis (Bacillus Tuberculosis);
* Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture;
* 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;
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis;
* Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial;