GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Study to Evaluate the Efficacy and Safety of GT90001 in Combination With Nivolumab as a Second-line Treatment in Subjects With Advanced Hepatocellular Carcinoma

Conditions
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HCC, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Nivolumab
* Drug: GT90001


Participation Criteria
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Eligibility Criteria
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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: 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 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;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GT90001+Nivolumab<br> | Drug: Nivolumab<br>* Nivolumab 240mg to be administered as an intravenous (IV) infusion every 2 weeks (Q2W).<br>* Other names: Opdivo, ONO-4538, BMS-936558, MDX1106;Drug: GT90001<br>* GT90001 7mg/kg to be administered as an intravenous infusion every 2 weeks (Q2W) after Nivolumab infusion.<br>* Other names: PF-03446962;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Objective Response Rate (ORR) (confirmed) as evaluated by an Independent Review Committee (IRC) according to RECIST v1.1 | 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 | Approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration OF Response (DOR) as evaluated by an IRC according to RECIST v1.1 |  | Approximately 2 years | 
| Progression Free Survival (PFS) as evaluated by an IRC according to RECIST v1.1 |  | Approximately 2 years | 
| Time To Response (TTR) as evaluated by an IRC according to RECIST v1.1 |  | Approximately 2 years | 
| Time to Progression (TTP) 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 | 
| ORR (confirmed) as evaluated by the investigator 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 | 
| TTR 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 | 
| DCR 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 | 
| 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 | 
| 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 | 
| ORR (confirmed) as evaluated by the investigator according to HCC mRECIST |  | Approximately 2 years | 
| DOR as evaluated by the investigator according to HCC mRECIST |  | Approximately 2 years | 
| PFS as evaluated by the investigator according to HCC mRECIST |  | Approximately 2 years | 
| TTR as evaluated by the investigator according to HCC mRECIST |  | Approximately 2 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 | 
| Overall survival (OS) |  | Approximately 3 years | 
| Safety and tolerability (any Advense Events (AEs), Severe AEs , immune-related AEs (irAEs), treatment-related AEs, abnormal laboratory values, etc. |  | 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 |