A Phase I Clinical Study to Evaluate the Efficacy and Safety of GB18 Injection in Patients With Tumor Cachexia

Key Inclusion Criteria:

* Voluntarily serve as a participant and sign the informed consent form;
* Age ≥ 18 years;
* Histologically or cytologically confirmed, non-resectable, locally advanced, recurrent, or metastatic solid tumors with failed standard treatment or have no standard treatment options. This includes, but is not limited to, colorectal cancer, pancreatic cancer, gastric cancer, esophageal cancer, biliary tract cancer, non-small cell lung cancer, prostate cancer, breast cancer, or ovarian cancer.
* Diagnosed with cancer cachexia: BMI \< 18.5 kg/m², and no unintentional weight loss \> 2% within 6 months before screening, or no unintentional weight loss \> 5% within 6 months before screening regardless of BMI.
* A serum GDF15 concentration ≥ 1.5 ng/mL.
* Laboratory Test Requirements:

  1. Absolute neutrophil count ≥ 1.0 × 10⁹/L, platelet count ≥ 75 × 10⁹/L, hemoglobin ≥ 80 g/L.
  2. Serum creatinine ≤ 1.5 × ULN (Upper Limit of Normal).
  3. Total bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 3 × ULN (or ≤ 5 × ULN for patients with liver metastasis).
  4. Activated partial thromboplastin time ≤ 1.5 × ULN, International Normalized Ratio ≤ 1.5.
  5. Left Ventricular Ejection Fraction \> 50% as assessed by echocardiogram.
* Eastern Cooperative Oncology Group (ECOG) performance status score: 0-2 points
* Expected survival period ≥ 4 months.

Key Exclusion Criteria:

* Known active/symptomatic central nervous system metastases and/or carcinomatous meningitis.
* Plan to receive radiotherapy as a component of the primary antitumor treatment regimen.
* BMI \> 26 kg/m².
* Presence of reversible causes for reduced food intake, including but not limited to NCI CTCAE grade 3 or 4 oral mucositis; NCI CTCAE grade 3 or 4 nausea, vomiting, diarrhea, or constipation; mechanical obstruction preventing oral intake.
* Comorbid conditions unrelated to tumor cachexia that cause difficulty in eating or malabsorption.
* Cachexia due to other investigator-determined or clearly defined causes. History within the past 6 months of any of the following: myocardial infarction, congenital long QT syndrome, second- or third-degree atrioventricular block, arrhythmias (including sustained ventricular tachycardia or ventricular fibrillation), unstable angina, acute coronary syndrome, symptomatic congestive heart failure (NYHA class III or IV) of coronary or peripheral origin, stroke, transient ischemic attack, or symptomatic pulmonary embolism or other clinically significant thromboembolic disease.
* Hypertension with unsatisfactory control despite antihypertensive therapy (defined as systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 90 mmHg).
* Patients receiving tube feeding or parenteral nutrition (total or partial) within 28 days before the first administration of the investigational drug.
* Initiation of new systemic glucocorticoid therapy from 28 days before the first dose of the investigational drug to the end of the study.
* Major surgery not yet recovered from within 28 days before the first dose of the investigational drug (central venous access placement and tumor biopsy are not considered major surgery), or anticipated major surgery during the study period.
* Prior participation in clinical trials targeting the GDF-15/GFRAL signaling pathways, or receipt of other investigational agents within 28 days or five half-lives (whichever is shorter) before the first dose of the investigational drug.
* Severe infection requiring intravenous antibiotics, antivirals, or antifungal agents within 14 days before the first dose of the investigational drug.