The purpose of this study is to evaluate the safety and efficacy of Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma

Jak inhibitors have already demonstrated the ability to reverse T-cell exhaustion in the treatment of Hodgkin lymphoma. Gecacitinib is a Jak inhibitor that has been approved for the treatment of bone marrow fibrosis. This study was designed to evaluate the safety and efficacy of Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma . Total 35 subjects will be recruited in this study, ORR will be will be used as primary outcome measures, OS, PFS, DCR and safety will be the secondary endpoints.

Inclusion Criteria:

1. Age and gender: >18 years old and≤75 years old, both men and women.
2. All subjects must have Hepatocellular Carcinoma confirmed by pathological or clinical diagnosis.
3. Patients with viable and measurable target lesion per RECIST 1.1.
4. Patients with unresectable hepatocellular carcinoma (uHCC) who experienced disease progression after first-line therapy containing immune checkpoint inhibitors.
5. Patients who are expected to live more than 3 months.

9.ECOG PS 0-1. 10.Child-Pugh ≤7.

Exclusion Criteria:

1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology.

2. History of malignant tumor, excluding the following cases:

   1. Malignant tumor that was curatively treated more than 5 years prior to study entry and has not recurred since then;
   2. Successful radical resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, preinvasive cervix carcinoma, and other preinvasive cancers.

3. Diffuse tumor lesion.

4. Preexisting or history of hepatic encephalopathy, hepatorenal syndrome or liver transplantation.

5. Clinically uncontrolled ascites or pleural effusion.

6. Received treatment with a JAK inhibitor previously .

7. Clinically severe gastrointestinal bleeding within 6 months of the start of treatment or any life-threatening bleeding events within 3 months of the start of treatment.