Durvalumab and Tremelimumab in Resectable HCC

Inclusion Criteria: For inclusion in the study, patients should fulfil the following criteria at time of study enrolment or when indicated: 1. Patient must be capable of providing written informed consent. 2. Age \>18 years at time of study entry 3. Histologically proven resectable HCC (early and intermediate stage HCC)\* 4. Must consent to provide biopsy sample prior to treatment 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 6. Childs Pugh score of 5 or 6 7. ALBI grade 1† 8. Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice, to ensure adequate viral suppression (HBV DNA ≤2000 IU/mL) prior to study entry. Patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (\<10 IU/ml or under limit of detection per local lab standard) do not require anti-viral therapy prior to study entry. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. 9. Patients with HCV infection must have management of this disease per local institutional practice throughout the study. HCV diagnosis is characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon enrollment. 10. Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. 11. Female of childbearing potential and non-sterilized male partners of a female patient of childbearing potential must agree to use effective method of contraception from the time of screening throughout the total duration of the drug treatment and 6 months after the last dose of study treatment. (See exclusion #22 for definition of effective method of contraception). 12. Adequate normal organ and marrow function as defined below within screening period: * Haemoglobin ≥9.0 g/dL * Absolute neutrophil count (ANC ≥1.0 × 109 /L) * Platelet count ≥65 × 109/L * Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). \<\<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. * AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal * Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 / 72 x serum creatinine (mg/dL) \- Albumin ≥2.8g/dl \- International normalized ratio ≤1. (for patients receiving Warfarin, please consult with the study physician) 13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 14. Body weight \> 30kg Exclusion Criteria: * 1\. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. 2\. Any prior therapy for HCC - except liver resection or ablation on one occasion only which was given with curative intent and that occurred at least two years prior to study enrolment. 3\. Evidence of distant metastasis co-existing malignant disease or macrovascular invasion on baseline imaging. 4\. History of hepatic encephalopathy within 12 months prior to enrolment or requirement for medications to prevent or control encephalopathy (no lactulose, rifaximin, etc, if used for purposes of hepatic encephalopathy). 5\. Evidence of portal vein thrombosis, visible on baseline/eligibility imaging, and patients with Vp1, Vp2, Vp3 and Vp4. 6\. Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first dose of study treatment. (a) Patients with ascites who have required pharmacologic intervention (eg, diuretics) and who have been on stable doses of diuretics for ascites for ≥2 months before enrolment are eligible. 7\. Any history of nephrotic or nephritic syndrome. 8. Evidence of symptomatic congestive heart failure (New York Heart Association II to IV) or symptomatic or poorly controlled cardiac arrhythmia. 9\. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[except for diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[e.g., granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, and uveitis\]). The following are exceptions to this criterion: (a) Patients with vitiligo or alopecia (b) Patients with hypothyroidism (e.g., following Hashimoto syndrome), stable on hormone replacement (c) Any chronic skin condition that does not require systemic therapy (d) Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician (e) Patients with celiac disease controlled by diet alone 10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease (ILD), serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase the risk of incurring AEs or compromise the ability of the patient to give written informed consent. 11\. History of another primary malignancy except for the following: 1. Prostate cancer of pathologic stage less than or equal to T2cN0M0 determined from a prior prostatectomy without biochemical recurrence and who, in the opinion of the Investigator, are not deemed to require active intervention, or patients with incidental histologic findings of prostate cancer that has not been treated prior to the study and who do not require specific therapy for prostate cancer beyond the surgery described in the Clinical Study Protocol and also are considered to be at low risk for recurrence per the Investigator 2. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence 3. Adequately treated non-melanoma skin cancer or lentigo malignant without evidence of disease 4. Adequately treated carcinoma in situ without evidence of disease 12. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 13\. Active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice) or human immunodeficiency virus (HIV; positive for HIV 1/2 antibodies). 14\. Active co-infection with both HBV and HCV, or co-infected with HBV and hepatitis D virus. 15\. Known allergy or hypersensitivity to any of the study treatments or any of the study treatment excipients. 16\. Major surgery (as defined by the Investigator) within 28 days prior to enrolment, or central venous access device placement within 7 days prior to enrolment (biopsy from any type of surgery within 28 days is not an exclusion criteria, nor are procedures to treat varices). 17\. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) 18. History of active primary immunodeficiency 19. History of allogeneic organ transplantation or those who are on a waiting list for liver transplantation. 20\. Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Patients, if enrolled, should not receive live vaccine while receiving study treatment and up to 90 days after the last dose of study treatment. 21\. Current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment. The following are exceptions to this criterion: (a) Intranasal, inhalational, topical steroids, or local steroid injections (e.g., intra-articular injection) (b) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent (c) Steroids as pre-medication for hypersensitivity reactions (e.g., CT-scan premedication) 22. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 6 months after the last dose of study treatment. Not engaging in sexual activity, per the patient's preferred and usual lifestyle, for the total duration of the treatment and 6 months after the last dose of study treatment is an acceptable practice.