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

Exclusion Criteria30

• Subjects who meet any of the criteria below must not be included:
• has received any of the anti-tumor treatments below:a) received cytotoxic chemotherapy, tumor immunotherapy, anti-tumor biologics or other trail agents within 4 weeks or 5 half-times (whichever is shorter) before the initial infusion.b)received an oral small-molecule targeted anti-tumor agent within 2 weeks before the first infusion or for five half-lives(whichever was shorter).c) received anti-tumor Chinese patent medicine approved by NMPA within 2 weeks before the initial infusion.d) received more than 30% bone marrow radiotherapy or large area radiotherapy within 2 weeks before initial infusion (palliative radiotherapy at the bone 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 interventional therapy (excluding tumor biopsy, puncture, etc.) within 4 weeks before initial infusion.
• unrecovered from the toxic reaction caused by previous anti-tumor treatment (not recovered to ≤ grade 1 or baseline; not including toxic reactions with no safety risk as determined by the investigator, such as alopecia, asymptomatic hypothyroidism caused by immune checkpoint inhibitors that can be treated with only thyroid hormone and remains stable, and etc.).
• with clinically uncontrollable serous effusion (pleural effusion, ascites and pericardio 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 ascites reinfusion, and etc.), or effusion obviously increased within 2 weeks after the local treatment and thus needs long-term catherterization. Candidates who meet any of the conditions above, or determined by the investigator as unsuitable, shall not be included.
• with central nervous system metastasis and show relating symptoms.
• with a history of other malignant tumors, except for those that have received radical surgery and not relapsed 5 years thereafter, such as carcinoma in situ of cervix, skin basal cell carcinoma, and etc.
• with a history of immune deficiency diseases, including acquired or congenital immunodeficiency disorders; or a history of organ transplantation, heterogeneous bone marrow transplantation, or autologous hematopoietic stem cell transplantation.
• had (non-infectious) lung inflammation / interstitial lung disease that required steroid treatment within 4 weeks before the initial infusion.
• with a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:
• severe abnormalty in cardiac rhythm or conduction, such as ventricular arrhythmia requiring clinical intervention, atrioventricular block of II~III grade, and etc.;
• cardiac insufficiency of III~IV grade as defined by New York Heart Association(NYHA);
• acute coronary syndrome, congestive cardiac failure, aortic dissection, cerebral stroke or other grade 3 or above cardio-cerebral vascular events within 6 months before the initial infusion.
• with uncontrollable high blood pressure (systolic pressure ≥160 mmHg and/or diastolic pressure ≥100 mmHg) after treatment with anti-hypertensive drugs of stable doses.
• 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 HCV RNA≥ lower limit of detection), or HIV infection.
• with active infections within 2 weeks before the initial infusion that require systematic treatment.
• with a history of active tuberculosis infection within 1 year before the initial infusion.
• had or has uncontrollable or serious diseases that may interfere with the participation 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 be considered infertilewhen they have been postmenopausal for at least 12 months) with positive results in serum pregnancy test; candidates of reproductive age (also including female spouse of reproductive age of male candidates), during the study or within 6 months after the last infusion, who will probably bear children, breastfeed, or are unwilling to cake effective contraceptives, as considered by the investigator.
• other conditions that are determined by the investigator as unsitable for entering this trial.
• For Expansion Cohort(Randomized, Double-blind, Placebo-controlled Part):
• 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 (excluding enteral nutrition support) within 28 days or 5 half-lives (whichever shorter) prior to 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 "symptomatic CNS metastases").
• Known allergy or contraindication to SXRN or its process impurities (e.g., spectinomycin).