a study of rag-01 in patients with non-muscle-invasive bladder cancer (nmibc) who have failed bacillus calmette guérin (bcg) therapy

Conditions: Non-Muscle-Invasive Bladder Cancer (NMIBC)

Summary: this is an open label, multi-center study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of rag-01 in patients with nmibc who have failed bcg therapy.

the study is planned to include a "3+3" dose escalation phase. the primary study period includes a screening period, a treatment and dose-limiting toxicity (dlt) assessment period, and a follow-up period.

Eligibility criteria:
inclusion criteria: 1. ability to understand the study and have signed the informed consent form; 2. ≥ 18, ≤ 75 years old, male or female; 3. pathologically confirmed high grade nmibc defined as grade 2 or grade 3 disease; 4. expected survival ≥ 6 months; 5. ecog ps ≤2; 6. sufficient organ functions, as defined below: investigations hematology absolute neutrophil count (anc): ≥ 1.5 x 109/l hemoglobin: ≥ 90 g/l platelet: ≥ 100 x 109/l liver function serum bilirubin: ≤ 1.25×uln or 2.5×uln（with gilbert syndrome） ast \& alt: ≤ 2.5×uln renal function creatinine clearance (cockcroft-gault equation): ≥ 30 ml/min 7. subject must be able to tolerate catheterization; 8. female subject of childbearing potential and her spouse must use adopt effective contraception (non-pharmacological contraception required) from signing informed consent to within 6 months after the last instillation. exclusion criteria: 1. subject who is allergy to rag-01 or similar products; 2. except for turbt, the subject received other anti-tumor treatments, and the last administration date is within ≤ 21 days or 5 half-lifes whichever is shorter from the date of signing icf; 3. subject with imaging examination diagnosed extravesical metastasis, including ureter and urethra; 4. subject has other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin, or adenocarcinoma of the prostate that has been surgically treated with a post-treatment psa that is non-detectable; 5. the following illnesses have not been relieved to ctcae 0-1: 1. uncontrolled acute and chronic infections, such as pneumonia, biliary tract infection, hepatitis b virus infection and hepatitis c virus infection; 2. dyspnea; 3. acute and chronic kidney injury, and inflammation; 4. urinary incontinence; 5. urinary frequency; 6. urinary tract obstruction (except benign prostatic hypertrophy); 6. subject could not hold the urine for at least 90 mins due to any reason; 7. new york heart association (nyha) 3 or 4 grade; 8. coronary heart disease related symptoms have not been relieved to ctcae 0-1, including: myocardial infarction, unstable angina pectoris, congestive heart failure and arrhythmia; 9. subject with qtc \>470 msec. 10. cerebrovascular accidents have not been relieved to ctcae 0-1; 11. hiv positive; active hepatitis b or c. for active hbv, it's defined as hbsag positive with hbv dna ≥ uln, for active hcv, it's defined as hcv antibody positive with hcv rna ≥ uln, respectively. 12. subject is pregnant or lactating during the treatment period; 13. history of central nervous system or psychiatric disorders, e.g., epilepsy or dementia; 14. other severe systemic diseases which might compromise the subject's compliance to the study, e.g., uncontrolled diabetes, gastrointestinal disorders, and renal diseases; 15. any other situations which are judged by the investigator, would exposure the subject to unnecessary risk, therefore he/she is not eligible.