Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)

Inclusion Criteria: 1. 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). 2. Measurable disease based on RECIST 1.1 3. HCC amenable to R0 resection with curable intent 4. Child-Pugh A liver disease 5. International normalised ratio (INR) ≤1.4 6. ECOG Performance status 0 or 1 7. Adequate haematological function as defined by: * Haemoglobin (Hb) \> 90g/l * Neutrophil Count \> 1.5 x 109/l * Platelets \> 75 x 109/l 8. Adequate renal function with GFR \>40ml/min using a validated creatinine clearance calculation (e.g. Cockcroft-Gault or Wright formula) 9. Adequate liver function as defined by: * Aminotransferase (ALT) or aspartate aminotransferase (AST) \< 5.0 x ULN * Albumin \>32g/l * Amylase ≤ 1.5 x ULN 10. 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. 11. 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 12. 18 years of age or over 13. Predicted life expectancy of \> 3 months 14. Patients must have given written informed consent 15. Patients must have the ability to swallow oral medication 16. Must be willing to use effective contraception during study for 120 days after last dose. Exclusion Criteria: 1. Has received any systemic chemotherapy, including anti-VEGF therapy, or any systemic investigational anticancer agents for advanced/unresectable HCC. 2. Has received local therapy including trans arterial embolic, chemo- or radiotherapy, external beam radiotherapy or ablative therapy to the measurable lesion to be resected. 3. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, or CD137). 4. Oesophageal or gastric variceal bleeding within the last 6 months. 5. Has received a live vaccine within 30 days prior to registration (seasonal flu vaccines that do not contain live virus are permitted). Administration of killed vaccines is allowed. 6. Active autoimmune disease that has required systemic treatment (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs) in past 2 years except * Vitiligo * Psoriasis * Autoimmune-related hyperthyroidism * Autoimmune-related hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone replacement therapy (e.g., levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 7. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 8. A diagnosis of immunodeficiency or is receiving systemic steroid therapy (\>10mg daily prednisolone equivalent) or any other form of immunosuppressive therapy within 7 days prior to treatment. 9. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 10. Has clinical or radiological evidence of ascites on physical examination that is not controlled with medication. 11. Uncontrolled blood pressure (Systolic BP)\>150 mmHg or diastolic BP \>90 mmHg) with no change in anti-hypertensive medications within 1 week prior to randomisation. 12. Has had clinically diagnosed hepatic encephalopathy in the last 6 months. 13. Has medical contraindications that preclude all forms of contrast enhanced imaging (tri-phasic CT or MRI). 14. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib. 15. Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula. 16. Clinically significant haemoptysis from any source or tumour bleeding within 2 weeks prior to start of treatment. 17. Electrolyte abnormalities that have not been corrected. 18. Significant cardiovascular impairment within 12 months of start of treatment such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of start of treatment, or cardiac arrhythmia requiring medical treatment at screening. 19. Prolongation of QTc interval to \> 480 ms. 20. Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO). 21. Patients who are at risk for severe haemorrhage, bleeding or thrombotic disorders, or are receiving factor X inhibitors or anticoa