Durvalumab Plus Lenvatinib as First-line Treatment for Unresectable Hepatocellular Carcinoma

Inclusion Criteria:

• Subjects volunteer to participate in the study and sign the informed consent beforeenrollment.
• 18-80 years of age.
• ECOG score of 0-1.
• Primary liver cancer with a pathological diagnosis of hepatocellular carcinoma.
• Child-Pugh grade A (5-6 points).
• BCLC C stage or BCLC B stage not suitable/refused for locoreginal treatments.
• Tumor volume ≤ 50% of the total liver volume.
• Without prior systemic therapy and unwilling to receive standard systemic therapy orunsuitable for standard systemic therapy.
• At least one measurable lesion as defined by RECIST v1.1 criteria.
• Patients infected with hepatitis virus should receive antiviral therapy regularly.
• No history of drug allergy.
• Function of vital organs in accordance with the following requirements (no bloodcomponents, cell growth factors and other corrective therapeutic agents are allowedwithin 14 days prior to enrolment): Absolute neutrophil count ≥ 1.5 x 10^9/L;Platelets ≥ 80 x 10^9/L; Haemoglobin ≥ 90 g/L; Serum albumin ≥ 35 g/L; Thyrotropin (TSH) ≤ 1×ULN (if abnormal, FT3 and FT4 levels should be examined at the same time, ifFT3 and FT4 levels are normal, enrollment is allowed); Serum bilirubin ≤ 1.5 x ULN (within 7 days prior to first dose); ALT and AST ≤ 5 x ULN (within 7 days prior tofirst dose); International normalised ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5x ULN; Serum creatinine ≤ 1.5 x ULN.
• Female patients who are non-surgically sterilised or of childbearing age are requiredto use contraception (e.g. IUD, pill or condom) during and for 3 months after the endof the treatment; female patients of childbearing age who are non-surgicallysterilised must have a negative serum or urine HCG test within 72h prior to studyentry; and must be non-lactating; male patients whose partners are women ofchildbearing age should be tested during the trial and for 3 months after the lastdose. Male patients whose partners are women of childbearing age should use aneffective method of contraception during the trial and for 3 months after the lastdose.

Exclusion Criteria:

• Patients with any active autoimmune disease or history of autoimmune disease (e.g. thefollowing but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis,enterocolitis, autoimmune hepatitis, pituitary inflammation, vasculitis, nephritis,hyperthyroidism, vitiligo. Patients with complete remission of asthma in childhood whodo not require any intervention in adulthood may be included, but those requirebronchodilators cannot be included.
• Patients who are on immunosuppressive drugs, or require systemic hormone therapy forimmunosuppression purposes (doses >10 mg/day of prednisone or other isotonic hormones)and who continue to use them within 2 weeks prior to enrollment.
• Receiving systemic therapy previously or other anti-cancer treatments (e.g.radiofrequency ablation, interventional therapy, radiotherapy, etc.)
• Patients with a known history of central neural system metastases or hepaticencephalopathy.
• Patients with clinically symptomatic ascites requiring puncture or drainage or thosewho have received ascites drainage within the previous 3 months.
• Patients with hypertension that is not well controlled by antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).
• Having clinical cardiac symptoms or disease not well controlled, such as (1) NYHAclass 2 or higher heart failure (2) unstable angina pectoris (3) myocardial infarctionwithin 1 year (4) clinically significant supraventricular or ventricular arrhythmiasrequiring treatment or intervention (5) QTc > 450 ms (men); QTc > 470 ms (women).
• With abnormal coagulation (INR > 2.0, PT > 16s), bleeding tendency or on thrombolyticor anticoagulant therapy. Prophylactic use of low-dose aspirin or low molecularheparin is allowed.
• Patients had clinically significant bleeding symptoms or a clear bleeding tendencywithin the 3 months prior to enrollment.
• Having arterial/venous thrombotic events within the 6 months prior to enrollment.
• With hereditary or acquired bleeding and thrombotic tendencies.
• With urine protein ≥ ++ and confirmed by 24-hour urine protein amount > 1.0 g.
• Patients with active infection, unexplained fever ≥ 38.5°C within 7 days prior to thefirst dose, or baseline white blood cell count > 15 x 10^9/L.
• Patient with a congenital or acquired immune deficiency (e.g. HIV infection).
• Patient with other malignancies (except cured basal cell carcinoma of the skin andcarcinoma in situ of the cervix) within the previous 3 years or concurrently.
• Patients who have other factors that could affect the outcome of the study or forcethe termination of the study, such as alcoholism, substance abuse, other seriousillnesses (including psychiatric illness) requiring comorbid treatment.