Pancreatic Cancer Clinical Trials

• Patients must meet all of the following criteria to be eligible for enrollment:

• 1\. Pancreatic cancer-specific inclusion criteria:

‣ Histologically or cytologically confirmed locally advanced or metastatic pancreatic ductal adenocarcinoma according to the TNM staging system of the International Association of Pancreatology and the 8th edition of the American Joint Committee on Cancer (AJCC);

‣ No prior systemic antitumor therapy for recurrent or metastatic disease;

‣ Prior adjuvant or neoadjuvant chemotherapy, radiotherapy, chemoradiotherapy, or immunotherapy for non-metastatic disease is allowed, provided that at least 6 months have elapsed since completion of the last treatment without disease recurrence;

‣ At least one measurable lesion according to RECIST version 1.1 (previously irradiated lesions may be considered measurable only if there is clear evidence of disease progression after radiotherapy).

• 2\. Fulfillment of Fearon criteria for cachexia or pre-cachexia:

• (1) Cachexia stage according to Fearon criteria: fulfillment of any of the following criteria in combination with decreased appetite (FAACT-A/CS 12 score ≤ 37) or systemic inflammation (CRP \> 5 mg/L):

• ① Unintentional weight loss \> 5% within the past 6 months;

⁃ Body weight loss \> 2% in patients with a BMI \< 18.5 kg/m². (2) Pre-cachexia stage according to Fearon criteria: all of the following three conditions must be met:

‣ ① Unintentional weight loss ≤ 5% within the past 6 months;

⁃ Systemic inflammation (CRP \> 5 mg/L);

‣ ③ Decreased appetite (FAACT-A/CS 12 score ≤ 37). 3. General inclusion criteria:

∙ Good compliance and provision of written informed consent;

∙ Age 18-75 years, regardless of sex;

∙ Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;

∙ Expected survival greater than 4 months;

∙ Adequate organ function, defined as follows:

• • Hematologic function: absolute neutrophil count ≥ 1.5 × 10⁹/L, hemoglobin ≥ 9 g/dL, platelet count ≥ 100 × 10⁹/L;

• • Hepatic function: total bilirubin ≤ 1.5 × upper limit of normal (ULN) (patients with known Gilbert's syndrome may be enrolled if serum bilirubin ≤ 3 × ULN), AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN in the presence of liver metastases), and alkaline phosphatase ≤ 3 × ULN (≤ 5 × ULN in the presence of liver or bone metastases); serum albumin ≥ 3 g/dL;

• • Coagulation function: international normalized ratio (INR), prothrombin time (PT), or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN;

• • Renal function: creatinine clearance ≥ 60 mL/min as calculated by the Cockcroft-Gault formula;

⁃ Urinary protein: urine protein ≤ 1+ on dipstick or 24-hour urine protein \< 1.0 g;

⁃ Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%.

∙ Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to first dosing (if a urine pregnancy test cannot be confirmed as negative, a serum pregnancy test is required and shall prevail). Women of childbearing potential who engage in sexual activity with non-sterilized male partners must use an acceptable method of contraception from screening and agree to continue contraception for 120 days after the last dose of study medication; decisions regarding discontinuation of contraception after this time point should be discussed with the investigator. Male patients who engage in sexual activity with women of childbearing potential must use effective contraception from screening until 120 days after the last dose of study medication; decisions regarding discontinuation of contraception after this time point should be discussed with the investigator.