A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study Evaluating the Efficacy and Safety of SXRN Injection in Patients With Cancer Cachexia

The subject must meet all the criteria below:

• 1. Male or female, aged 18\~75 at the time of signing the ICF;
• 2. Histologically or cytologically confirmed advanced malignancy of one of the following: pancreatic cancer; non-small cell lung cancer (NSCLC); colorectal cancer;

• 3. Disease status and prior treatment history (meet any one of the following):

  1. Pancreatic cancer: Locally advanced (unresectable) or metastatic pancreatic ductal adenocarcinoma, with treatment failure after at least 2 lines of prior systemic anti-tumor therapy (may include gemcitabine, nab-paclitaxel, irinotecan, platinum agents, and fluoropyrimidines);
  2. Non-small cell lung cancer (NSCLC): Stage IIIB/IV NSCLC, with treatment failure after at least 2 lines of prior systemic anti-tumor therapy (must include platinum-based chemotherapy; patients with positive driver gene must have received corresponding targeted therapy);
  3. Colorectal cancer: Metastatic colorectal cancer, with treatment failure after at least 3 lines of prior systemic anti-tumor therapy (must include fluoropyrimidines, oxaliplatin, and irinotecan); patients with MSI-H/dMMR tumors must have received anti-PD-1/PD-L1 therapy followed by treatment failure.

• 4. Diagnosis of cancer anorexia-cachexia based on the cachexia staging criteria from the 2025 Chinese Guidelines for the Diagnosis and Treatment of Cancer Anorexia-Cachexia Syndrome with consideration of Chinese population characteristics, i.e., satisfying the following criteria (either ①② or ①③):

  1. Involuntary weight loss >5% in 6 months; OR weight loss >2% when BMI \<18.5 kg/m²; OR weight loss >2% accompanied by muscle mass depletion;
  2. Anorexia (VAS score ≤70, or FAACT-A/CS-12 score ≤37);
  3. CRP>5 mg/L;
• 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
• 6. Expected survival time ≥12 weeks;
• 7. Lab results and organ function tested within 7 days before the initial infusion meet the following criteria:

Complete Blood Count: Absolute Neutrophil Count (ANC) ≥ 1.0×109/L; Platlets (PLT) Count ≥ 75×109/L; Hemoglobins (Hb) ≥ 80 g/L.

Note: Subjects with chronic anemia caused by underlying tumor or cachexia may be enrolled if the investigator assesses the condition as stable; anemia resulting from active bleeding is excluded.

Blood Biochemistry: Total bilirubin (TBIL) ≤3.0 × upper limit of normal (ULN); Serum creatinine (SCr) ≤1.5 × ULN or creatinine clearance (CrCl) by Cockroft-Gault formula ≥30 mL/min; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN; for subjects with concurrent liver metastases, AST and ALT ≤5.0×ULN and ALP ≤6.0×ULN;

Blood coagulation function: International Normalized Ratio (INR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN.

Note: for subjects receiving precautious anti-coagulation treatment, the investigator shall determine whether INR and APTT remains in a safe and effective range for treatment.

Echocardiogram: Left Ventricular Ejection Fraction (LVEF) ≥50%;

• 8. Subjects are capable of understanding and voluntarily signing the written informed consent form (ICF); subjects must be willing and able to complete study procedures and follow-up assessments.

Exclusion Criteria:

Subjects who meet any of the criteria below must not be enrolled:

• 1. Reversible causes of reduced food intake as determined by the investigator, which may include but are not limited to mechanical obstruction resulting in patients' inability to eat;
• 2. Patients who have received any appetite-enhancing or weight-loss-improving medications (including marketed prescription drugs and investigational clinical trial agents) within 28 days before the first study drug administration or 5 half-lives of the drug (whichever is shorter), including but not limited to anamorelin, progestogens such as medroxyprogesterone acetate, cannabinoids, and medical cannabis;
• 3. Patients who are only able to receive tube feeding and parenteral nutrition and cannot take oral food intake;
• 4. Patients with cachexia clearly attributable to other underlying conditions, such as severe chronic obstructive pulmonary disease (COPD), AIDS, etc.;
• 5. Hormonal therapies judged by the investigator to have effects for improving tumor anorexia-cachexia;
• 6. Patients who have undergone major surgery or interventional procedures within 4 weeks prior to the first dose, or who are scheduled to undergo such procedures during the trial (excluding tumor biopsy, puncture, etc.);
• 7. Patients with toxicities from previous antitumor therapies that have not yet recovered to ≤ Grade 2 or baseline levels (except for toxicities judged by the investigator as to pose no safety risk, such as alopecia, or asymptomatic hypothyroidism induced by immune checkpoint inhibitors that is stable and only requires thyroid hormone replacement therapy);
• 8. Clinically uncontrolled serous cavity effusion (pleural effusion, ascites, pericardial effusion): moderate or greater effusion; local therapy (including drainage, peritoneal shunt, cell-free concentrated ascites reinfusion therapy, etc.) within 2 weeks before screening or planned within 2 weeks; significant effusion increase within 2 weeks after local therapy; requirement for long-term indwelling catheter. Subjects meeting any condition or deemed by the investigator unsuitable for enrollment will be excluded;
• 9. Patients with central nervous system metastases requiring intervention;
• 10. History of other malignancies, except for those who have undergone curative treatment with no recurrence within 5 years, such as carcinoma in situ of the cervix, basal cell carcinoma of the skin, etc.;
• 11. History of immunodeficiency, including acquired or congenital immunodeficiency diseases, organ transplantation, allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation;
• 12. (Non-infectious) pulmonary inflammation/interstitial lung disease requiring steroid therapy within 4 weeks prior to the first infusion;

• 13. Subjects with a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

  1. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second- to third-degree atrioventricular block, etc.;
  2. Subjects with New York Heart Association (NYHA) Class III-IV cardiac dysfunction;
  3. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade ≥3 cardiovascular and cerebrovascular events occurring within 6 months prior to the first study drug administration;
• 14. Hypertension uncontrolled by a stable regimen of antihypertensive medication (systolic blood pressure ≥160 mmHg, and/or diastolic blood pressure ≥100 mmHg);
• 15. Subjects with active chronic hepatitis B (e.g., HBsAg positive or HBcAb positive with HBV DNA above the lower limit of detection), active hepatitis C (e.g., HCV antibody positive with HCV RNA above the lower limit of detection), or human immunodeficiency virus (HIV) infection;
• 16. Active infection requiring systemic therapy within 2 weeks prior to the first dose;
• 17. History of active tuberculosis infection within 1 year prior to the first dose;
• 18. Any other uncontrolled or significant comorbid disease(s), either currently or historically, that by the investigator's judgment may interfere with trial participation or evaluation;
• 19. Known allergy or contraindication to the investigational product (SXRN injection) or its drug substance process-related impurities (e.g., spectinomycin);
• 20. For premenopausal female participants (postmenopausal females must be amenorrheic for at least 12 months to be considered of non-childbearing potential): subjects with positive serum pregnancy test, or participants of childbearing potential (including female partners of male participants) who, in the investigator's opinion, are likely to become pregnant, are breastfeeding, or are unwilling to use effective contraception during the study and for at least 6 months after the last dose of the study drug;
• 21. Any other condition that considered by the investigator as to render the patient unsuitable for participation in the study.