Combination of Sintilimab and Stereotactic Body Radiotherapy in Advanced Metastatic HCC

Inclusion Criteria:

1. Histologically confirmed hepatocellular carcinoma or diagnosed by American Associationfor the Study of Liver Disease criteria;

2. Deemed ineligible for curative intent therapy with surgical resection or livertransplantation.

3. Estimated life expectancy ≥12 weeks;

4. Male or female subjects with age: 18-70 years old

5. Failure in first-line systemic treatment with sorafenib or Lenvatinib

6. Unwilling to receive or unable to tolerate first-line treatment with sorafenib

7. Have ECOG performance status 0-1

8. Have measurable disease based on RECIST 1.1.

9. Pretreatment CT chest /abdomen /pelvis within 28 days of protocol enrollment.

10. Child-Pugh class A liver function (assessed within 14 days of SBRT)；

11. The function of important organs meets the following requirements: a. white blood cellcount (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L; b. platelets ≥ 50×109/L; c. hemoglobin ≥ 8g/dL; d. serum albumin ≥ 3.0g/dL; e. total bilirubin ≤ 2.0×ULN, ALT, AST ≤ 5×ULN; f. serum creatinine ≤ 1.5×ULN

12. Must have at least one lesion amenable to SBRT.

13. Ability to understand the study and sign informed consent.

Exclusion Criteria:

1. A history of abdominal radiotherapy;

2. Presence of active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit ofthe assay);

3. Active autoimmune diseases, a history of autoimmune diseases (including but notlimited to these diseases or syndromes, such as colitis, hepatitis, hyperthyroidism),a history of immunodeficiency (including a positive HIV test result)

4. History of organ transplantation or allogeneic bone marrow transplantation，or otheracquired or congenital immunodeficiency diseases

5. Receipt of live, attenuated vaccine within 30 days prior to the study treatment

6. Has a known history of active TB (Bacillus Tuberculosis).

7. Uncontrolled intercurrent illness including, but not limited to digestive tract ulcer,uncontrolled hypertension, fracture, uncured wound, history of congestive heartfailure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/socialsituations that would limit compliance with study requirements

8. Prior invasive malignancy within 2 years except for noninvasive malignancies such ascervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of theskin, lobular or ductal carcinoma in situ of the breast that has been surgically cured

9. Female patients who are pregnant or lactating

10. Untreated central nervous system (CNS) metastatic disease, lepto-meningeal disease, orcord compression

11. Active infection requiring systemic therapy

12. Presence of clinically meaningful ascites，hydrothorax or hydropericardium and patientsrequiring non pharmacologic intervention (eg, paracentesis) or escalation inpharmacologic intervention to maintain symptomatic control

13. Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)