GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma
- Conditions
- HCCHepatocellular Carcinoma
- Interventions
- Registration Number
- NCT05178043
- Lead Sponsor
- Suzhou Kintor Pharmaceutical Inc,
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 5
- 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.
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Presence of tumor thrombus involving main trunk of portal vein (Vp4), inferior vena cava, cardiac involvement of HCC;
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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;
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History of encephalopathy;
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Has a known history of, or any evidence of central nervous system (CNS) metastases and/or carcinomatous meningitis;
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Had history of a solid organ or hematologic transplant;
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Has received locoregional therapy to liver (TACE, TAE, hepatic arterial infusion [HAI], radiation, radioembolization or ablation) within 4 weeks of start of study treatment.
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Had prior systemic TKI treatment prior to start of study treatment;
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Has received prior immune checkpoint inhibitors within 4 weeks of start of study treatment;
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Has received Nivolumab in the first-line systemic therapy:
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Active co-infection with:
- Both hepatitis B and C as evidenced by positive HBV surface antigen or detectable HBV DNA and HCV RNA, OR
- Hepatitis D infection in subjects with hepatitis B
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Has an active bacterial or fungal infection requiring systemic therapy within 7 days prior to study drug dosing;
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Has a known history of active tuberculosis (Bacillus Tuberculosis);
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Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture;
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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;
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Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
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Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis;
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Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description GT90001+Nivolumab GT90001 - GT90001+Nivolumab Nivolumab -
- Primary Outcome Measures
Name Time Method The Objective Response Rate (ORR) (confirmed) as evaluated by an Independent Review Committee (IRC) according to RECIST v1.1 Approximately 2 years ORR is defined as the proportion of participants with best overall response of confirmed complete response (CR) or partial response (PR). RECIST: Response Evaluation Criteria in Solid Tumors
- Secondary Outcome Measures
Name Time Method Time To Response (TTR) as evaluated by an IRC according to RECIST v1.1 Approximately 2 years DOR as evaluated by the investigator according to RECIST v1.1 Approximately 2 years PFS as evaluated by the investigator according to RECIST v1.1 Approximately 2 years TTP as evaluated by the investigator according to RECIST v1.1 Approximately 2 years ORR (confirmed) as evaluated by an IRC according to HCC mRECIST Approximately 2 years TTR as evaluated by an IRC according to HCC mRECIST Approximately 2 years TTP as evaluated by an IRC according to HCC mRECIST Approximately 2 years DCR as evaluated by an IRC according to HCC mRECIST Approximately 2 years Duration OF Response (DOR) as evaluated by an IRC according to RECIST v1.1 Approximately 2 years Disease Control Rate (DCR) as evaluated by an IRC according to RECIST v1.1 Approximately 2 years DCR as evaluated by the investigator according to RECIST v1.1 Approximately 2 years TTR as evaluated by the investigator according to HCC mRECIST Approximately 2 years DOR as evaluated by an IRC according to HCC mRECIST Approximately 2 years PFS as evaluated by an IRC according to HCC mRECIST Approximately 2 years DOR as evaluated by the investigator according to HCC mRECIST Approximately 2 years Presence of Anti-Drug Antibodies (ADAs) to GT90001 and Nivolumab during the study relative to the presence of ADAs at baseline Approximately 2 years Time to Progression (TTP) as evaluated by an IRC according to RECIST v1.1 Approximately 2 years ORR (confirmed) as evaluated by the investigator according to RECIST v1.1 Approximately 2 years ORR (confirmed) as evaluated by the investigator according to HCC mRECIST Approximately 2 years Progression Free Survival (PFS) as evaluated by an IRC according to RECIST v1.1 Approximately 2 years TTR as evaluated by the investigator according to RECIST v1.1 Approximately 2 years PFS as evaluated by the investigator according to HCC mRECIST Approximately 2 years Overall survival (OS) Approximately 3 years TTP as evaluated by the investigator according to HCC mRECIST Approximately 2 years DCR as evaluated by the investigator according to HCC mRECIST Approximately 2 years Safety and tolerability (any Advense Events (AEs), Severe AEs , immune-related AEs (irAEs), treatment-related AEs, abnormal laboratory values, etc. Approximately 2 years
Trial Locations
- Locations (5)
NYU Langone Health
🇺🇸New York, New York, United States
Los Angeles Hematology Oncology Medical Group
🇺🇸Los Angeles, California, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Renovatio Clinical
🇺🇸Houston, Texas, United States
Medical Oncology Associates
🇺🇸Spokane, Washington, United States