Advanced hepatocellular carcinoma
Conditions
Interventions
Experimental Group:Apalolithovolrelimab combined with bevacizumab and HAIC
Sponsors
Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Willing to participate in this study and sign the informed consent form. 2. Age between 18 and 75 years (inclusive). 3. Pathologically or clinically diagnosed with primary hepatocellular carcinoma, or recurrence after curative resection for primary hepatocellular carcinoma; classified as stage 2–3 according to the Chinese Liver Cancer Staging System (CNLC), or B/C stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system, and assessed by the investigator as unsuitable for surgery. 4. Liver function status evaluated as Child-Pugh A based on clinical and laboratory data during screening, or Child-Pugh B that has been downgraded to Child-Pugh A following liver-protective treatment. 5. Patients classified as Vp1–Vp2 according to the Japan Liver Cancer Research Group classification (Vp classification). 6. No prior systemic anti-tumor therapy, including monotherapy or combination therapy with immune checkpoint inhibitors. 7. At least one measurable lesion (according to RECIST v1.1 or mRECIST criteria). 8. ECOG performance status score of 0–1. 9. Adequate organ function meeting the following requirements (excluding use of blood components or growth factors during screening): (1) white blood cell count >=3.0×10^9/L; (2) absolute neutrophil count >=1.5×10^9/L; (3) platelet count >=80×10^9/L; (4) hemoglobin >=9 g/dL; (5) serum albumin >=3 g/dL; (6) thyroid-stimulating hormone (TSH) =60 mL/min (calculated using the standard Cockcroft-Gault formula); (10) urinalysis showing urine protein <2+; for patients with urine protein 2+ at baseline, a 24-hour urine collection is required, with 24-hour urinary protein quantification <1 g; (11) coagulation function: international normalized ratio (INR) <=2 or prothrombin time (PT) within 6 seconds above the upper limit of normal. 10. For HBsAg-positive patients, HBV DNA must be <2000 IU/mL or <10^4 copies/mL, and effective antiviral therapy with entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, or emtricitabine must be continued throughout the study period. Patients with a history of HCV infection but negative PCR results for HCV RNA may be considered non-infected. 11. Female participants of childbearing potential must confirm they are not pregnant before enrollment. All enrolled patients (male or female) must use adequate contraception throughout the treatment period and for 4 weeks after treatment completion.
Exclusion criteria
Exclusion criteria: 1. Patients with sarcomatoid HCC, mixed cell carcinoma, or fibrolamellar cell carcinoma; those with other active malignant tumors other than HCC within 5 years or concurrently; and those with HCC with three or more metastatic sites or with brain metastases. 2. Those who have previously received allogeneic stem cell or solid organ transplantation. 3. Those with a history of gastrointestinal bleeding within 6 months before the start of the study treatment; those with portal hypertension and patients with a high risk of bleeding as determined by the investigator (including those with moderate to severe esophageal and gastric varices with a risk of bleeding, active local gastrointestinal ulcers, and persistent positive fecal occult blood), who need to undergo gastroscopy to rule out patients with "red signs". If there is a history of "red signs" in gastroscopy, they should be excluded from the study. 4. Those who have experienced abdominal fistula, gastrointestinal perforation, or abdominal abscess within 6 months before the start of the study treatment. 5. Those with known hereditary or acquired bleeding disorders (such as coagulation disorders) or thrombotic symptoms. 6. Those who have experienced thrombosis or any grade of arterial or venous thromboembolic events within 6 months before the start of the study treatment. 7. Those with hypertension that cannot be well controlled with antihypertensive drugs (systolic blood pressure>= 160 mmHg or diastolic blood pressure >= 100 mmHg); those with a history of hypertensive crisis or hypertensive encephalopathy. 8. Those with major vascular diseases within 6 months before the start of the study treatment (including but not limited to coronary atherosclerotic heart disease, acute myocardial infarction, aortic dissection, cerebral thrombosis, cerebral hemorrhage, etc.). 9. Those with severe, unhealed or open wounds and active ulcers. 10. Those who have undergone surgery within 4 weeks before the start of the study treatment. 11. Those with a history of or current pulmonary fibrosis, organizing pneumonia (such as obliterative bronchiolitis), interstitial pneumonia, pneumoconiosis, drug-related pneumonia, or idiopathic pneumonia. 12. Those with any active autoimmune disease or a history of autoimmune disease with recurrence during the treatment period. 13. Those with any contraindications to HAIC treatment, bevacizumab, PD-1 inhibitors, CTLA-4 inhibitors, or FOLFOX regimens. 14. Those who have received live attenuated vaccines within 28 days before the start of the study treatment, or those who are expected to receive such vaccines during the treatment period with PD-1 immune inhibitors or within 60 days after the last dose of PD-1 immune inhibitors. 15. Those with a known history of human immunodeficiency virus (HIV) infection. 16. Those who have received other investigational drugs within 28 days before the start of the study treatment. 17. Pregnant, lactating, or women planning to become pregnant during the study period. 18. Those with other conditions that the investigator deems unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective remission rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Median progression-free survival period;Disease control rate;Median overall survival period;Incidence rate of adverse events; | — |
Countries
China
Contacts
Public ContactXiujun Cai
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
Outcome results
None listed