A Phase I, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Evaluate the Safety and Efficacy of T3011 in Patients With BCG-Failure Non-Muscle-Invasive Bladder Cancer (NMIBC)
This is a prospective, open-label, single-arm investigator-initiated clinical study. It is used to evaluate the safety and efficacy of T3011 intravesical instillation in patients with BCG-failure high-risk non-muscle invasive bladder cancer (NMIBC)
• Participants who understand and voluntarily sign the written ICF, and are willing and able to comply with all trial requirements.
• Male or female, aged ≥ 18 years at the time of signing the ICF.
• Participants with a histologically confirmed diagnosis of NMIBC (Ta, T1 and/or Tis).
• Participants with high risk NMIBC who have been diagnosed by cystoscopy, urine cytology, and histopathology within 8 weeks prior to the first dose administration and have failed or intolerant to BCG treatment after TURBT surgery, and are not suitable or willing to undergo radical cystectomy.
• BCG-failure include BCG refractory, recurrence or relapsing after BCG treatment, BCG unresponsive and BCG intolerant.
• All tumors should have no visible tumors after transurethral bladder tumor resection (TURBT). If meeting the requirements for secondary resection, secondary resection need to be done. It is recommended to perform secondary resection if the following conditions are met: the first TURBT is insufficient, there is no muscle tissue in the first resection specimen (excluding low-grade \[Ta G1\] tumors and pure in situ cancers), T1 stage tumors, and high-grade \[G3\] tumors (excluding pure in situ cancers); Secondary resection is recommended to be performed 2-6 weeks after the first resection; Participants undergoing secondary resection must meet the requirement of no visible tumors after surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Expected survival ≥3 months.
• Sufficient hematology and terminal organ function were met within 4 weeks prior to the first s treatment, for example, having sufficient bone marrow reserves and organ function:
‣ Hematology (hematopoietic growth factor treatment or blood transfusion should not be given within 2 weeks prior to the treatment of study drug): ANC≥1.5×10\^9/L, PLT count ≥75×10\^9/L, Hemoglobin (HGB) ≥90 g/L.
⁃ Renal function: Creatinine clearance ≥60 mL/min (based on Cockcroft-Gault equation for calculation)
⁃ Hepatic function: Serum total bilirubin (TBIL) ≤1.5×ULN, Aspertate aminotransferase (AST) and alanine transaminase (ALT) ≤3×ULN
⁃ Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN; Activated partial thromboplastin time (aPTT) ≤1.5×ULN
⁃ Women with fertility should agree to use contraceptive measures (such as intrauterine devices (IUDs), contraceptives, or condoms) during the study period and within 6 months after the end of the study; Within 7 days prior to enrollment in the study, the serum or urine pregnancy test was negative and must be a non lactating patient; Men should agree to patients who must use contraceptive measures during the study period and within 6 months after the end of the study period. Note: A female subject with fertility is defined as a female subject who has not reached a postmenopausal state after menarche (continuous amenorrhea for at least 12 months, with no other clear cause other than menopause), and has not undergone surgery (i.e. bilateral ovariectomy, fallopian tube resection, and/or hysterectomy) or other causes determined by the researcher (such as underdeveloped Mullerian tubes) leading to permanent infertility.