A Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)

AN OPEN LABEL, SINGLE ARM PHASE 1B STUDY OF AVELUMAB PLUS AXITINIB AS FIRST LINE TREATMENT IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA

To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first line treatment in patients with advanced HCC

Inclusion Criteria:

• Diagnosis of locally advanced or metastatic HCC, obtained by histology/cytology (on a prior tumor biopsy) or by imaging with serum α-fetoprotein (AFP) ≥400 ng/mL.
• All patients must provide at least 1 archival tumor specimen. If archival tumor specimen is no longer available, de novo tumor biopsy will be required during screening.
• HCC not amenable to local therapy.
• Measurable disease according to RECIST v. 1.1.
• Child Pugh Class A disease.
• BCLC stage B or C disease.
• No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart.
• ECOG performance status 0 or 1.
• Adequate bone marrow function, renal and liver functions
• Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) as assessed by multigated acquisition (MUGA) scan or echocardiogram (ECHO).

Exclusion Criteria:

• Prior systemic treatment for advanced HCC, including prior treatment with approved or investigational drugs.
• Any prior locoregional therapy within 4 weeks and radiotherapy or surgical procedure within 2 weeks (4 weeks for major surgery) of enrollment.
• Patients with known symptomatic brain metastases requiring steroids.
• Presence of hepatic encephalopathy (ie, Child Pugh score of 2 or 3) and/or clinically relevant ascites (ie, Child Pugh score of 3).
• Presence of main portal vein invasion by HCC.
• Any of the following within the 12 months prior to enrollment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular accident, transient ischemic attack.
• Active infection requiring systemic therapy except for hepatitis C virus (HCV) and hepatitis B virus (HBV).