| Eligibility |
Inclusion Criteria:
1. Age =18 years but =75 years
2. Resectable HCC staged BCLC A/B
3. Treatment naïve for HCC
4. High risk for recurrence, meeting at least one of the following criteria:
1. Multiple tumor lesions
2. Individual tumor > 5cm
3. AFP > 400 ug/L
4. MVI positive based on preoperative MRI according to MVI predictive model of
Radiomics
5. Measurable or evaluable lesions according to RECIST v1.1 criteria
6. ECOG performance status 0-1
7. Child-Pugh class A
8. Life expectancy = 12 weeks
9. Adequate organ and marrow function as defined below:
1. Hemoglobin =9.0 g/dL
2. Absolute neutrophil count = 1,500/µL
3. Platelets count = 75,000/µL
4. Total serum bilirubin = 1.5 ×upper limit of normal(ULN)
5. AST and ALT = 5 × ULN, ALP = 4 ×ULN
6. Serum creatinine = 1.5 ×ULN
7. INR = 1.5 ×ULN, APTT = 1.5 ×ULN
8. Serum albumin =3.0 g/dL
10. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test.
11. Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen as assessed by the treating investigator are eligible for this
trial.
12. Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
1. Any prior treatment for HCC.
2. Tumor rupture or bleeding. Suspected abdominal metastasis.
3. A major surgical procedure, open biopsy, or significant traumatic injury with poorly
healed wound within 6 weeks prior to enrollment.
4. History of allogenic organ transplantation.
5. Under other clinical trials.
6. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this
criterion: vitiligo or alopecia, hypothyroidism (e.g., following Hashimoto syndrome)
stable on hormone replacement, any chronic skin condition that does not require
systemic therapy or celiac disease controlled by diet alone.
7. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to AK104 or other immune checkpoint inhibitors.
8. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection (including tuberculosis), uncontrolled hypertension (defined as blood
pressure of > 140/90 mmHg during the screening period despite medical management),
interstitial lung disease, serious chronic gastrointestinal conditions associated with
diarrhea, or psychiatric illness/social situations that would limit compliance with
study requirement, substantially increase risk of incurring AEs, or compromise the
ability of the patient to give written informed consent.
9. History of hepatic encephalopathy, refractory ascites or esophagogastric varices with
high risk of bleeding. Upper gastrointestinal hemorrhage within the year prior to the
first dose of study drug.
10. Active hepatitis B infection without treatment (positive HBV surface antigen (HBsAg)
and HBV DNA = 1000 IU/ml). Patients with a past or resolved HBV infection (defined as
the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
eligible. Active hepatitis C infection (positive HCV antibody and HCV RNA above the
lower limit of detection).
11. A primary brain tumor (excluding meningiomas and other benign lesions), any brain
metastases, leptomeningeal disease, seizure disorders not controlled with standard
medical therapy, or history of a stroke within the year prior to the first dose of
study drug.
12. History of active primary immunodeficiency.
13. History of testing positive for human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS)
14. Current or prior use of immunosuppressive medication within 14 days prior to the first
dose of study agent. The following are exceptions to this criterion: Intranasal,
inhaled, topical steroids, or local steroid injections (e.g., intra-articular
injection). Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day
of prednisone or its equivalent. Steroids as premedication for hypersensitivity
reactions (e.g., CT scan premedication).
15. Receipt of live attenuated vaccine within 30 days prior to the first dose of study
drug. Note: Patients, if enrolled, should not receive live vaccine whilst receiving
study drug and for at least 30 days after the last dose of study agent.
16. Systemic immunostimulant therapy within 14 days prior to the first dose of study
agent.
17. History of serious systemic disease, including myocardial infarction or unstable
angina within the 12 months prior to the first dose of study drug, hypertensive crisis
or hypertensive encephalopathy, New York Heart Association (NYHA) grade II or greater
congestive heart failure, unstable symptomatic arrhythmia requiring medication,
significant vascular disease or symptomatic peripheral vascular disease.
18. History of coagulopathy, bleeding diathesis, or thrombosis within the 12 months prior
to the first dose of study drug.
19. A serious, non-healing wound, ulcer, or bone fracture.
20. Pregnancy or lactation.
21. Total parenteral nutrition.
22. Exclusion from the study by the judgement of investigators, due to some factors that
may lead to the forced termination of the study, including other acute, chronic or
psychological disease.
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