Safety, Tolerability, and Preliminary Efficacy of BH011 in Subjects With Non-Muscle-Invasive Bladder Cancer

Korábbi kezelés

• Patients who have not recovered (toxicity assessment remains > Grade 1 or has not recovered to baseline levels) from toxic reactions (other than malaise, alopecia) associated with prior antineoplastic therapy; patients who have not recovered to Grade 0-1 (CTCAE 5.0) within 3 days prior to the first dose for the following: uncontrolled acute and chronic infections, e.g., pneumonitis, biliary tract infections, hepatitis B virus infections, and hepatitis C virus infections; Respiratory distress; acute and chronic kidney injury; nephrotic syndrome; bladder perforation; urinary tract obstruction.
• Patients previously treated with docetaxel.
• Patients with previous extensive radiotherapy to the pelvis (radiotherapy > 30% of the bone marrow area).
• Patients who have undergone major surgical treatment within 28 days prior to the first dose, or who have failed to recover to ≤ grade 2 from adverse effects of any such procedure.
• Patients who have received intravesical therapy within 28 days prior to the first dose (immediate chemotherapy infusion after previous and current electrodes is permitted).
• Patients receiving antitumor therapy such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, biologic therapy, and herbal medicine within 28 days or 5 half-lives of the drug, whichever is longer, prior to the first dose.
• Patients who have participated in any other clinical interventional trial treatment (other than patients enrolled in a study with overall survival follow-up) within 28 days or 5 half-lives, whichever is longer, prior to the first dose.
• Patients who plan to receive other anticancer treatments or other investigational drugs during the study period.
• Pregnant or breastfeeding female patients. Positive blood pregnancy test in females of childbearing potential within 7 days prior to first dose; Any male and female patient of childbearing potential refuses to use a contraceptive method with an annual failure rate of <1% (contraceptive methods with an annual failure rate of <1% include bilateral tubal ligation, male sterilization, proper use of hormonal contraceptives that suppress ovulation, hormone-releasing intrauterine devices (IUDs), and copper-containing IUDs, or condoms) throughout the duration of the trial and for a period of 30 days after the last study dose. In the judgment of the investigators, a patient is defined as having the ability to procreate as he/she is biologically capable of having children as well as having a normal sex life. Female patients who are not of childbearing potential (i.e., meet at least 1 of the following criteria):
  • Has had a hysterectomy or bilateral oophorectomy, or
  • Medically diagnosed with ovarian failure, or
  • Medically diagnosed as post-menopausal (menopause for at least 12 consecutive months in the absence of pathologic or physiologic causes).

Más betegség

• Patients with muscle-invasive bladder cancer (T2-T4).
• Patients with a history of vesicoureteral reflux.
• Patients with other malignancies within 2 years, except locally curable (cured) cancers, e.g. basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix.
• Patients with uncontrolled hypertension on treatment (defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg).
• Patients with known or suspected hypersensitivity to docetaxel, its excipients or similar drugs.
• Patients with known history of psychiatric disorders, substance abuse, drug and alcohol addiction, and impairments in adherence.

Laborértékek

• Patients with severe or uncontrolled cardiac disease requiring treatment, including: a) severe arrhythmias (ventricular arrhythmias requiring clinical intervention, degree II-III atrioventricular block, etc.); b) history of myocardial infarction, unstable angina pectoris, angioplasty, or coronary artery bridging surgery within 6 months prior to the first dose of the study drug; c) New York Heart Association (NYHA) class III or IV congestive heart failure (see Appendix 4); d) 12-lead electrocardiography: corrected QTc intervals: QTc > 450 ms in men and QTc > 470 ms in women (QTc intervals were calculated using the Fridericia formula).

Egyéb

• Patients with urothelial carcinoma of the upper or lower urinary tract, and/or lymph node metastases.
• Patients with peripheral neuropathy > grade 1.
• Any other patients who, in the opinion of the investigator, would result in unnecessary risk to the subject and are therefore unsuitable for participation in this clinical study.

• Subjects were fully informed about the study and voluntarily signed an informed consent form and were willing to complete the trial in accordance with the protocol process.
• Male or female, ≥18 years of age at time of informed consent.
• First TURBT completed within 12 weeks prior to the first dose, histologically confirmed diagnosis of non-muscle invasive bladder cancer and classified as high risk according to the European Association of Urology 2020 version of the Non-Muscle Invasive Bladder Cancer Guidelines.
• Patients who had failed intravesical administration of BCG prior to enrolment and were not candidates for or refused radical cystectomy.BCG failures included BCG refractory, recurrence after BCG, BCG non-responsive, and BCG intolerant;
• After TURBT, it is confirmed that the tumour has been completely removed from the bladder. A second TURBT is required for the following: confirmed or suspected incomplete resection of the tumour by TURBT; absence of muscularis propria tissue in the first resection of the tumour specimen, except for TaLG/G1 tumours or primary carcinoma in situ; and stage T1 bladder tumours. A second TURBT is recommended 2 to 6 weeks after the initial TURBT.
• Eastern Cooperative Oncology Group (ECOG) score 0 to 1.
• Expected survival ≥ 6 months.
• The major organs are functioning well, i.e. the following criteria are met:
  • Bone marrow function: hemoglobin (HGB) ≥80 g/L, platelet count (PLT) ≥100×109/L, absolute neutrophil count (ANC) ≥1.5×109/L.
  • Liver function: serum total bilirubin ≤ 1.25 x upper limit of normal (ULN) (or 2.5 × ULN in case of constitutional hepatic dysfunction jaundice [Gilbert's syndrome]), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN.
  • Renal function: creatinine clearance ≥30 mL/min (Cockcroft-Gault formula) or serum creatinine ≤2.0 mg/dL.