A Phase I Study on Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of SXRN Plasmid DNA Technique in Patients With Advanced Solid Tumors

For Dose-Escalation Phase:

• Inclusion Criteria:

• male or female, aged 18~75 at the time of signing the ICF;

• patient with advanced solid tumors who have failed/cannot tolerate previous standardtherapies or lack conventional effective therapies;

• at least one measurable or evaluable lesion according to Response EvaluationCriteria in Solid Tumors (RECIST, version 1.1);

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;

• expected survival time ≥12 weeks;

• lab results and organ function tested within 7 days before the initial infusion meetthe criteria below:

• Blood routine: 1)Absolute Neutrophil Count (ANC) ≥1.5×10^9/L;2)Platlets (PLT)Count≥90×10^9/L; 3)Hemoglobins (Hb) ≥90 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 Gaultformula ≥50 mL/min; 3)Aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT) ≤2.5×ULN; for participants with liver metastasis, AST, ALT≤5.0×ULN, andALP≤6.0×ULN; d)Albumin (ALB) ≥30g/L.

• Urine protein ≤2+ (if >2+, urine protein shall be collected for 24 hours; totalprotein ≤1g is acceptable for inclusion).

• International Normalized Ratio (INR), Prothrombin Time (PT), Activated PartialThromboplastin 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.

• Left Ventricular Ejection Fraction (LVEF) ≥50%.

• can understand and voluntarily sign the Informed Consent Form (ICF); must bevoluntary and able to finish the study program and follow-up tests.

Exclusion Criteria:

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

• has received any of the anti-tumor treatments below:a) received cytotoxicchemotherapy, tumor immunotherapy, anti-tumor biologics or other trail agents within 4 weeks or 5 half-times (whichever is shorter) before the initialinfusion.b)received an oral small-molecule targeted anti-tumor agent within 2 weeksbefore the first infusion or for five half-lives(whichever was shorter).c) receivedanti-tumor Chinese patent medicine approved by NMPA within 2 weeks before theinitial infusion.d) received more than 30% bone marrow radiotherapy or large arearadiotherapy within 2 weeks before initial infusion (palliative radiotherapy at thebone or superficial lesions is acceptable).

• participated in and received an investigational drug or device clinical trial within 4 weeks before initial infusion.

• Patients who had undergone or planned to undergo major surgery or interventionaltherapy (excluding tumor biopsy, puncture, etc.) within 4 weeks before initialinfusion.

• unrecovered from the toxic reaction caused by previous anti-tumor treatment (notrecovered to ≤ grade 1 or baseline; not including toxic reactions with no safetyrisk as determined by the investigator, such as alopecia, asymptomatichypothyroidism caused by immune checkpoint inhibitors that can be treated with onlythyroid hormone and remains stable, and etc.).

• with clinically uncontrollable serous effusion (pleural effusion, ascites andpericardio effusion). Conditions may include: moderate or above sized effusion,received within 2 weeks before the selection or plans to receive local treatments (including drainage, peritoneal shunt, and cell-free concentrated ascitesreinfusion, and etc.), or effusion obviously increased within 2 weeks after thelocal treatment and thus needs long-term catherterization. Candidates who meet anyof the conditions above, or determined by the investigator as unsuitable, shall notbe included.

• with central nervous system metastasis and show relating symptoms.

• with a history of other malignant tumors, except for those that have receivedradical surgery and not relapsed 5 years thereafter, such as carcinoma in situ ofcervix, skin basal cell carcinoma, and etc.

• with a history of immune deficiency diseases, including acquired or congenitalimmunodeficiency disorders; or a history of organ transplantation, heterogeneousbone marrow transplantation, or autologous hematopoietic stem cell transplantation.

• had (non-infectious) lung inflammation / interstitial lung disease that requiredsteroid treatment within 4 weeks before the initial infusion.

• with a history of severe cardiovascular and cerebrovascular diseases, including butnot limited to:

1. severe abnormalty in cardiac rhythm or conduction, such as ventriculararrhythmia requiring clinical intervention, atrioventricular block of II~IIIgrade, and etc.;

2. cardiac insufficiency of III~IV grade as defined by New York HeartAssociation(NYHA);

3. acute coronary syndrome, congestive cardiac failure, aortic dissection,cerebral stroke or other grade 3 or above cardio-cerebral vascular eventswithin 6 months before the initial infusion.

• with uncontrollable high blood pressure (systolic pressure ≥160 mmHg and/ordiastolic pressure ≥100 mmHg) after treatment with anti-hypertensive drugs of stabledoses.

• with active chronic hepatitis B (such as, HbsAg or HbcAb positive and HBV DNA ≥lower limit of detection, active hepatisis C (such as, HCV antibody positive and HCVRNA≥ lower limit of detection), or HIV infection.

• with active infections within 2 weeks before the initial infusion that requiresystematic treatment.

• with a history of active tuberculosis infection within 1 year before the initialinfusion.

• had or has uncontrollable or serious diseases that may interfere with theparticipation or evaluation in the study, as considered by the investigator;

• known to be allergic or taking drugs contradictionary to the study drug (Suplussirna) or its excipients.

• premenopause female candidates (postmenopausal female patients can only beconsidered infertilewhen they have been postmenopausal for at least 12 months) withpositive results in serum pregnancy test; candidates of reproductive age (alsoincluding female spouse of reproductive age of male candidates), during the study orwithin 6 months after the last infusion, who will probably bear children,breastfeed, or are unwilling to cake effective contraceptives, as considered by theinvestigator.

• other conditions that are determined by the investigator as unsitable for enteringthis trial.

For Expansion Cohort(Randomized, Double-blind, Placebo-controlled Part):

• Inclusion Criteria:

• Male or female, aged 18 to 75 years at time of signing ICF.

• Histologically or cytologically confirmed solid tumor.

• Patients who have failed standard therapy, lack standard therapy, or are in atreatment holiday period (4 weeks) without need for anti-tumor therapy.

• Diagnosis of cancer anorexia-cachexia according to 2025 CSCO guideline, meetingeither (①+②) or (①+③):

• Involuntary weight loss >5% in 6 months; OR weight loss >2% with BMI <18.5kg/m²; OR weight loss >2% with reduced muscle mass.

• Anorexia (VAS ≤70 or FAACT-A/CS-12 score ≤37).

• CRP >5 mg/L.

• ECOG performance status 0-2.

• Life expectancy ≥12 weeks.

• Adequate organ function and laboratory parameters within 7 days prior to first studydrug, meeting the same criteria as listed above for the dose-escalation phase (i.e.,ANC, platelets, hemoglobin, liver/kidney function, coagulation, LVEF, etc.).

• Same informed consent requirement as the dose-escalation phase: able to understandand voluntarily sign the ICF, and willing/able to complete study procedures andfollow-up.

Exclusion Criteria:

The exclusion criteria are the same as those for the dose-escalation phase above, with the following additional or modified criteria:

• Reversible causes of reduced food intake determined by investigator (e.g.,mechanical obstruction preventing eating).

• Use of any medication or therapy for cachexia, anorexia, or weight loss (excludingenteral nutrition support) within 28 days or 5 half-lives (whichever shorter) priorto first study drug, including but not limited to progestins (megestrol acetate,medroxyprogesterone acetate), corticosteroids, anamorelin, cannabinoids, androgens,NSAIDs.

• Currently receiving tube feeding or parenteral nutrition.

• Cachexia clearly due to other causes (e.g., severe COPD, AIDS).

• Hormone therapy judged by investigator to improve cachexia.

• Central nervous system metastases requiring intervention (instead of "symptomaticCNS metastases").

• Known allergy or contraindication to SXRN or its process impurities (e.g.,spectinomycin).

• Note: For the expansion cohort, the washout period for other investigational drugsis "4 weeks or 5 half-lives" (same as dose-escalation phase), and all otherexclusion criteria (prior anti-tumor treatments, unresolved toxicity, serouseffusion, cardiovascular disease, infections, etc.) apply identically as listedabove.