PRIMER-1 Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)
This is a multicentre randomised 3-arm phase II clinical trial in patients with resectable Hepatocellular Carcinoma (HCC). Sixty patients will be randomized 1:1:1 to 6 weeks of pre-operative therapy with: pembrolizumab, lenvatinib or the combination of pembrolizumab and lenvatinib followed by up to 12 months treatment with post-operative pembrolizumab. The aim of the study is to compare the efficacy of pembrolizumab combined with lenvatinib with that of pembrolizumab and lenvatinib alone in terms of major pathological response in patients with resectable HCC. Major pathological response will be defined by the proportion of patients with less than 10% viable tumour at resection.
• Have a diagnosis of Hepatocellular Carcinoma (HCC) confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) and suitable for surgical resection. Radiological confirmation of diagnosis is provided by the study site and defined by the presence of a liver mass of at least 1 cm and exhibiting arterial hypervascularity with washout in the portal venous phase seen in a tri-phasic magnetic resonance imaging (MRI).
• Measurable disease based on RECIST 1.1
• HCC amenable to R0 resection with curable intent
• Child-Pugh A liver disease
• International normalised ratio (INR) ≤1.4
• ECOG Performance status 0 or 1
• Adequate haematological function as defined by:
‣ Haemoglobin (Hb) \> 90g/l
⁃ Neutrophil Count \> 1.5 x 109/l
⁃ Platelets \> 75 x 109/l
• Adequate renal function with GFR \>40ml/min using a validated creatinine clearance calculation (e.g. Cockcroft-Gault or Wright formula)
• Adequate liver function as defined by:
‣ Aminotransferase (ALT) or aspartate aminotransferase (AST) \< 5.0 x ULN
⁃ Albumin \>32g/l
⁃ Amylase ≤ 1.5 x ULN
⁃ Patients with past or ongoing hepatitis C virus (HCV) infection will be eligible for the study if HCV viral load is undetectable at screening. The treated patients must have completed their treatment curative anti-viral treatment at least 4 weeks prior to randomisation.
⁃ Patients with controlled hepatitis B will be eligible as long as they meet the following criteria:
∙ Antiviral therapy for hepatitis B virus (HBV) must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL prior to randomisation. Patients on active HBV therapy with viral loads under 500 IU/mL should stay on the same therapy throughout study treatment.
‣ Patients who are positive for anti-hepatitis B core antibody (HBc), negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV viral load under 500 IU/mL, do not require HBV anti-viral prophylaxis
⁃ 18 years of age or over
⁃ Predicted life expectancy of \> 3 months
⁃ Patients must have given written informed consent
⁃ Patients must have the ability to swallow oral medication
⁃ Must be willing to use effective contraception during study for 120 days after last dose.