gt90001 plus nivolumab in patients with advanced hepatocellular carcinoma

Conditions: Hepatocellular Carcinoma; HCC

Summary: 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;