A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of SXRN Injection in Patients With Cancer Cachexia

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of SXRN Injection in Patients With Cancer Cachexia

This is a clinical study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of SXRN Injection in cancer patients with anorexia-cachexia. Phase Ia employs a single-arm, open-label, dose-escalation design. Phase Ib, an extension of the study, utilizes a design of combination therapy with standard anti-tumor therapy for cancers including but not limited to pancreatic cancer, non-small cell lung cancer (NSCLC), and colon cancer.

This study is collaboratively sponsored by Jiangsu Nutai Biologics Co., Ltd. and Jiangsu GQ Co., Ltd.. Nutai serves as the Responsible Party for this registration.

Inclusion Criteria:

Participants must meet all the following criteria for inclusion:

• 1. Male or female, aged 18 to 75 years (inclusive) at the time of signing the informed consent form (ICF);

• 2. Patients with histologically or cytologically confirmed advanced solid tumors, with at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;

• 3. Diagnosed of cancer anorexia-cachexia based on the 2025 Guidelines for the Diagnosis and Treatment of Cancer Anorexia-Cachexia Syndrome and referring to Chinese population characteristics, i.e., meeting the following criteria (either ① + ② or ① + ③):

  ① >5% involuntary weight loss within the past 6 months; or >2% weight loss if BMI <18.5 kg/m²; or >2% weight loss in the presence of reduced muscle mass;

  ② Anorexia (VAS score ≤70, or FAACT-A/CS score ≤37);

  ③ CRP >5 mg/L;

• 4. (Phase Ia only) Cancer patients who have failed or are intolerant (experienced drug-related ≥ Grade 4 hematologic toxicity, or ≥ Grade 3 non-hematologic toxicity) to prior standard therapy, or lack effective conventional treatment options;

• 5. (Phase Ib only) Patients requiring standard anti-tumor drug therapy per CSCO guidelines of advanced pancreatic cancer, non-small cell lung cancer, colorectal cancer, or other eligible solid tumors;

• 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;

• 7. Life expectancy ≥12 weeks.

• 8. Laboratory test results and organ function assessed within 7 days prior to the first dose must meet the following criteria:

• Blood routine: 1)Absolute Neutrophil Count (ANC) ≥1.5×10^9/L;2)Platlets (PLT) Count≥75×10^9/L; 3)Hemoglobins (Hb) ≥80 g/L.

Note: the criteria above shall still be maintained within 14 days before the initial infusion, either without the need of blood transfusion, or using supportive treatment including granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), interleukin-11 (IL-11), and erythropoietin (EPO), and etc.

• Blood biochemistry: 1)Total bilirubin (TBIL) ≤3.0 × upper limit of normal (ULN); 2)Serum creatinine (SCr) ≤1.5 × ULN or creatinine clearance (CrCl) by Cockroft Gault formula ≥30 mL/min; 3)Aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT) ≤3×ULN; for participants with liver metastasis, AST, ALT≤5.0×ULN, and ALP≤6.0×ULN; d)Albumin (ALB) ≥30g/L.
• Urine routines: Urine protein ≤2+ (if >2+, 24-hour urine protein quantification must be performed, and total protein ≤1 g is required for eligibility).
• Blood coagulation: 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.

• Ultrasonic cardiogram: Left Ventricular Ejection Fraction (LVEF) ≥50%.
• 9.The participant must be able to understand and voluntarily sign the written Informed Consent Form (ICF); and must be willing and able to comply with all study procedures and follow-up examinations.

Exclusion Criteria:

Participants meeting any of the following criteria shall be excluded from the study:

• 1. Reversible causes of reduced food intake as determined by the investigator, which may include but are not limited to mechanical obstruction preventing adequate oral intake;

• 2. Use of any prescription medication intended to improve appetite or mitigate weight loss within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of the investigational product, including but not limited to anamorelin, megestrol acetate, cannabinoids, or medical marijuana;

• 3. Patients currently receiving tube feeding or parenteral nutrition support;

• 4. Treatment with any other investigational drug within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose of the study drug;

• 5. Patients with cachexia clearly attributable to other underlying conditions, such as severe chronic obstructive pulmonary disease (COPD), AIDS, etc.;

• 6. Hormonal therapy judged by the investigator as potentially to improve the assessment of cachexia-related outcomes.

• 7. 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.);

• 8. Patients with toxicities from previous antitumor therapies that have not yet recovered to ≤ Grade 1 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);

• 9. Clinically uncontrolled third-space fluid accumulation (e.g., pleural effusion, ascites, or pericardial effusion), meeting any of the following criteria: moderate or larger volume, received local treatment (including drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy, etc.) within 2 weeks before screening or scheduled within the next 2 weeks, significant re-accumulation within 2 weeks after local treatment, or requiring long-term catheterization; or judged by the investigator as unsuitable for enrollment;

• 10.Patients with central nervous system metastases requiring intervention;

• 11.History of other malignancies, except for those who have undergone curative treatment with no recurrence within 5 years (e.g., carcinoma in situ of the cervix, basal cell carcinoma of the skin, etc.);

• 12.History of immunodeficiency, including acquired or congenital immunodeficiency diseases, organ transplantation, allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation;

• 13.(Non-infectious) pulmonary inflammation/interstitial lung disease requiring steroid therapy within 4 weeks prior to the first infusion;

• 14.History of severe cardiovascular or cerebrovascular diseases, including but not limited to:

  1. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second- or third-degree atrioventricular block, etc.;
  2. Cardiac dysfunction classified as Class III-IV per the New York Heart Association (NYHA) criteria;
  3. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular/cerebrovascular events within 6 months prior to the first dose;

• 15.Hypertension uncontrolled by a stable regimen of antihypertensive medication (systolic blood pressure ≥160 mmHg, and/or diastolic blood pressure ≥100 mmHg);

• 16.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;

• 17.Active infection requiring systemic therapy within 2 weeks prior to the first dose;

• 18.History of active tuberculosis infection within 1 year prior to the first dose;

• 19.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;

• 20.Known allergy or contraindication to the investigational product (SXRN injection) or its drug substance process-related impurities (e.g., spectinomycin);

• 21.For premenopausal female participants (postmenopausal females must be amenorrheic for at least 12 months to be considered of non-childbearing potential): serum pregnancy test as positive, 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 investigational product;

• 22. Any other condition that considered by the investigator as to render the patient unsuitable for participation in the study.