Nanocrystalline Megestrol Acetate Versus Placebo for Anorexia in Patients With Unresectable Hepatocellular Carcinoma Receiving TACE Combined With Targeted and Immunotherapy

Inclusion Criteria:

* Patients with unresectable primary hepatocellular carcinoma (HCC) confirmed by imaging or histopathology
* No previous receipt of immunotherapy and/or targeted drug therapy
* Child-Pugh score ≤ 7
* At least one measurable lesion per RECIST 1.1 criteria; lesions without prior radiotherapy, cryotherapy or other local treatment
* Single intrahepatic lesion \< 10 cm, or fewer than 10 intrahepatic lesions with tumor burden \< 50%
* Meet precachexia criteria: non-volitional weight loss ≤ 5% in 6 months, plus systemic inflammation (CRP \> 5 mg/L) or decreased appetite (FAACT-A/CS-12 score ≤ 37 points)
* Meet cachexia criteria: accompanied by decreased appetite or systemic inflammation, with either non-volitional weight loss \> 5% in 6 months or BMI \< 18.5 kg/m² plus weight loss \> 2%
* Voluntarily participate and sign informed consent
* Age ≥ 18 years, male or female
* Able to swallow tablets normally
* ECOG performance status 0 or 1
* Life expectancy ≥ 12 weeks
* Adequate major organ function without blood products or colony-stimulating factors within 14 days
* Hematology: ANC ≥ 1.5×10⁹/L, Hb ≥ 80 g/L, PLT ≥ 50×10⁹/L
* Liver function: TBIL ≤ 1.5×ULN, AST/ALT ≤ 5.0×ULN, ALB ≥ 28 g/L
* Coagulation function: INR, PT or aPTT ≤ 1.5×ULN
* Renal function: SCr ≤ 1.5×ULN or creatinine clearance ≥ 60 mL/min
* Urine protein ≤ 1+ or 24-hour urine protein \< 1.0 g
* Cardiac function: LVEF ≥ 50%
* Females of childbearing potential with negative pregnancy test within 3 days before first dosing
* Fertile male and female patients agree to effective contraception from screening to 120 days after last study drug
* HBV/HCV infected patients receive stable antiviral therapy without drug interaction

Exclusion Criteria:

* Active or untreated CNS metastases; inadequately controlled metastatic brain or leptomeningeal disease
* Uncontrolled tumor-related pain
* Thromboembolic disease, ascites or lower limb edema within 6 months
* History of other malignancies within 5 years before randomization, except curable low-risk tumors
* Unresolved adverse toxicities from prior antitumor therapy not recovered to ≤ Grade 1 (CTCAE v5.0), excluding alopecia
* Pregnant, breastfeeding females or those planning pregnancy during the study
* Any unstable medical, psychiatric or social condition that may interfere with study participation
* Positive HIV infection
* Major surgery within 28 days prior to randomization
* Severe cardiovascular disease, myocardial infarction, unstable arrhythmia, angina or cerebrovascular events
* Severe systemic infection within 4 weeks before dosing or active infection requiring systemic anti-infective treatment
* Impaired gastrointestinal absorption, long-term tube feeding, parenteral nutrition or eating disorders
* Concomitant use of other appetite-enhancing or weight-stimulating agents
* Cushing's syndrome, adrenal or pituitary insufficiency, poorly controlled diabetes
* Uncontrolled hypertension despite oral antihypertensive treatment
* Esophagogastric varices, severe ulcers, gastrointestinal bleeding, obstruction, perforation or fistula within 6 months
* Known hypersensitivity to any component of the investigational product
* Any other condition considered inappropriate for enrollment by the investigator.