Study Efficacy and Safety of INC280 in Patients With Advanced Hepatocellular Carcinoma.

• Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 [ Time Frame: baseline, 6 weeks up to 6 months ] [ Designated as safety issue: No ]
  Time to progression is the time from the date of baseline evaluation to the date of the first documented radiological confirmation of disease progression or death due to underlying cancer.
  
  

• Overall Response Rate [ Time Frame: baseline, every 6 weeks up to 6 months ] [ Designated as safety issue: No ]
  Overall Response Rate is defined as the proportion of patients with a best overall response of complete response or partial response at any time on study per RECIST version 1.1.
  
  
• Progression free survival [ Time Frame: date of treatment, every 6 weeks up to 6 months ] [ Designated as safety issue: No ]
  Progression free survival is defined as the time from date of first study treatment intake to the date of the first radiologically documented progression or death due to any cause or initiation of new antineoplastic therapy. if a patient has not had an event, progression free survival is censored at the date of last adequate tumor assessment.
  
  
• Overall survival [ Time Frame: From date of treatment until death, average 10.7 months ] [ Designated as safety issue: No ]
  Overall survival is defined as the time from date of first study treatment intake to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.
  
  
• Disease Control Rate [ Time Frame: baseline, every 6 weeks up to 6 months ] [ Designated as safety issue: No ]
  Disease control rate is defined as the proportion of patients with a best overall response of complete response, partial response or stable disease at any time on study per RECIST version 1.1
  
  
• Safety: adverse events, serious adverse events [ Time Frame: From baseline until 30 days post study treatment ] [ Designated as safety issue: Yes ]
  Frequency, duration and severity of adverse events.
  
  
• Safety: hematology and chemistry values, vital signs, electrocardiograms [ Time Frame: From baseline until end of treatment, average 6 months from baseline ] [ Designated as safety issue: Yes ]
  Change from baseline values.
  
  
• Tolerability of study drug [ Time Frame: From date start of treatment until end of treatment, average 6 months from baseline ] [ Designated as safety issue: Yes ]
  Tolerability will be assessed by summarizing the number of dose interruptions, dose reductions and dose intensity.
  
  
• Plasma pharmacokinetic parameter: AUC0-t [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ] [ Designated as safety issue: No ]
  Plasma concentration of INC280 versus time profiles. AUC=Area Under the Curve
  
  
• Alpha-fetoprotein [ Time Frame: baseline, every 6 weeks up to 6 months ] [ Designated as safety issue: No ]
  Change from baseline
  
  
• Soluble c-MET [ Time Frame: baseline, Cycle 1 Days 1, 2 and 15, then Day 1 of each cycle until end of treatment ] [ Designated as safety issue: No ]
  Change from baseline
  
  
• Soluble Hepatocyte Growth Factor [ Time Frame: baseline, Cycle 1 Days 1, 2 and 15, then Day 1 of each cycle until end of treatment ] [ Designated as safety issue: No ]
  Change from baseline
  
  
• Plasma pharmacokinetic parameter: CL/F [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ] [ Designated as safety issue: No ]
  Plasma concentration of INC280 versus time profiles
  
  
• Plasma pharmacokinetic parameter: Cmax [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ] [ Designated as safety issue: No ]
  Plasma concentration of INC280 versus time profiles. Cmax = Maximum concentration
  
  
• Plasma pharmacokinetic parameter: Tmax [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ] [ Designated as safety issue: No ]
  Plasma concentration of INC280 versus time profiles. Tmax =Time to reach maximum concentration
  
  
• Plasma pharmacokinetic parameter: T1/2 [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ] [ Designated as safety issue: No ]
  Plasma concentration of INC280 versus time profiles
  
  
• Plasma pharmacokinetic parameter: Racc [ Time Frame: Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 ] [ Designated as safety issue: No ]
  Plasma concentration of INC280 versus time profiles
  
  

This study is designed as a Phase II, single arm, open-label, multicenter study to evaluate the safety and efficacy of INC280 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for or had disease progression after surgical or locoregional therapies, with c- MET dysregulation.

The study includes a Dose-Determining Part and a Dose Expansion Part. Pharmacokinetic and safety profiles of INC280 in the setting of liver dysfunction will be determined in the Dose-Determining Part. The Dose Expansion Part will start when the appropriate dose for patients with liver dysfunction is determined based on pharmacokinetics (PK) and safety data from the Dose-Determining Part and other INC280 ongoing clinical studies.