A Phase II, Single-arm, Multicenter, Prospective Study of Cadonilimab and Lenvatinib for Conversion Therapy in Unresectable Hepatocellular Carcinoma
This study is a single-arm, open-label, exploratory clinical trial designed to assess the effectiveness and safety of the combination therapy of Cadonilimab and Lenvatinib for conversion treatment in unresectable hepatocellular carcinoma. Eligible patients, meeting the inclusion criteria and providing informed consent, will undergo 3-4 cycles of Cadonilimab and Lenvatinib conversion therapy. A single imaging assessment will be conducted, and successfully converted patients will proceed to surgical treatment, with pathological evaluation of intraoperative specimens. Post-surgery, patients will choose an appropriate adjuvant treatment based on prior treatment benefits, disease baseline, and personal preferences. Patients who do not successfully convert and experience disease progression will exit the study for alternative treatment. Those who do not successfully convert but do not exhibit disease progression will continue conversion treatment with Cadonilimab and Lenvatinib±TACE/HAIC, with tumor imaging assessments every 3 cycles. Successfully converted patients will undergo surgery, followed by the selection of an appropriate adjuvant treatment based on prior treatment benefits, disease baseline, and personal preferences. Patients who do not successfully convert and experience disease progression will exit the study for alternative treatment. Those who do not successfully convert but do not exhibit disease progression will continue conversion treatment with Cadonilimab and Lenvatinib±TACE/HAIC until disease progression or intolerable toxicity occurs, with a maximum treatment duration of 2 years. Efficacy assessment will use mRECIST and RECIST v1.1 criteria, and safety evaluation will follow CTCAE 5.0 standards. Adverse events will be recorded throughout the study, with a period extending to 60 days after treatment completion for serious adverse events or those related to Enfortumab Vedotin, and in some cases extended to 90 days post-treatment.
• Participants must sign a written informed consent form before enrollment. Age \>18 and ≤75 years, both genders are eligible. Patients with histologically or pathologically confirmed hepatocellular carcinoma (HCC) or meeting the clinical diagnostic criteria for HCC according to the American Association for the Study of Liver Diseases (AASLD).
⁃ BCLC stage C without distant or lymphatic metastasis, or BCLC stage B ineligible for curative surgical treatment.
⁃ Presence of measurable lesions (according to RECIST 1.1 criteria, CT scan long diameter ≥10 mm for non-lymph node lesions, CT scan short diameter ≥15 mm for lymph node lesions).
⁃ No prior systemic anticancer therapy. No prior local treatment for target lesions, including TAE, TACE, TARE, surgery, ablation, PEI, or radiotherapy.
⁃ Child-Pugh score \<7. ECOG PS score: 0-1. At least one untreated measurable lesion according to RECIST v1.1, or a measurable lesion with confirmed progression after local treatment (e.g., radiofrequency ablation, ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, arterial embolization, arterial chemoembolization, etc.) per mRECIST criteria.
⁃ Expected survival \>12 weeks. Non-surgically sterilized or premenopausal female patients must use a medically approved contraceptive measure during the study treatment period and within 3 months after the end of the study treatment. Pregnancy tests for non-surgically sterilized premenopausal female patients must be negative within 7 days before study entry, and they must not be lactating. Non-surgically sterilized or fertile male patients must agree to use a medically approved contraceptive measure with their female partners during the study treatment period and within 3 months after the end of the study treatment.
⁃ Adequate organ function, excluding any blood component and growth factor use within 14 days:
⁃ Hematology: ANC ≥1.5×10\^9/L, PLT ≥50×10\^9/L, HGB ≥90g/L. Liver function: TBIL ≤3×ULN, ALT and AST ≤5×ULN, serum albumin ≥28 g/L, ALP ≤5×ULN, and must be stable for at least 1 week after routine liver protection treatment as assessed by the investigator.
⁃ Renal function: Cr ≤1.5×ULN or creatinine clearance ≥50 mL/min (using the standard Cockcroft-Gault formula), and urine protein \<2+; for patients with baseline urine protein ≥2+, a 24-hour urine collection and quantitative measurement with \<1g of protein is required.
⁃ Coagulation function: INR and APTT ≤1.5×ULN; for subjects receiving anticoagulant therapy, PT and INR should be within the planned range.