Non-muscle invasive bladder cancer
Conditions
Interventions
Phase Ia JL19001 Monotherapy Dose Escalation Group:JL19001 Injection Intravesical Administration (Dose Escalation: 100, 200, 400 µg/week)
Phase Ib JL19001 Combined with BCG Dose Escalation Group:JL19001 Injection Combined with BCG Intravesical Administration (Dose Escalation: 1/4, 1/2, 1 x RDC Combined with BCG 120mg)
Phase II Cohort 1 (BCG-naive):JL19001 Injection (RDE) Combined with BCG (120mg) Intravesical Administration
Phase II Cohort 2 (BCG-refractory CIS):JL19001 Injection (RDE) Combined with BCG (120mg) Intravesical Administration
Phase II Cohort 3 (BCG-refractory Ta/T1):JL19001 Injection (RDE) Combined with BCG (120mg) Intravesical Administration
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Able to understand and voluntarily sign the informed consent form, and cooperate to complete the visits specified in the protocol; 2. Age >= 18 years at the time of signing the informed consent form, regardless of gender; 3. Expected survival time >= 2 years; 4. Eastern Cooperative Oncology Group (ECOG) performance status score <= 2; 5. Previous pathological tissue biopsy diagnosed as high/very high risk NMIBC, NMIBC grading details see Table 4; (1) Stage Ia/Ib 1) BCG-unresponsive CIS; 2) BCG-unresponsive Ta/T1; (2) Stage II 1) Cohort 1: BCG-naive, referring to patients who have not previously received BCG intravesical instillation therapy; 2) Cohort 2: BCG-unresponsive CIS; 3) Cohort 3: BCG-unresponsive Ta/T1; Note: BCG-unresponsive is defined as at least one of the following: 1) BCG-refractory: High-grade tumor detected within 6 months after adequate BCG therapy, or tumor progression in grade/stage 3 months after 1 BCG treatment cycle; 2) BCG-relapsing: Recurrence of high-grade tumor after maintaining tumor-free status for 6 months following adequate BCG therapy (within 6-9 months after the last BCG treatment). Adequate BCG therapy is defined as at least one of the following: 1) Completion of at least 5 out of 6 initial induction instillations (recommended dose per package insert) plus at least 2 out of 3 maintenance instillations; 2) Completion of at least 5 out of 6 initial induction instillations (recommended dose per package insert) plus at least 2 out of 6 second induction instillations; 6. Cystoscopy within 6 weeks before first dose shows complete resection of lesions or residual lesions only as CIS; For T1 stage lesions, postoperative pathological results must show the presence of bladder muscle tissue; 7. Subjects voluntarily choose not to undergo radical cystectomy after fully understanding the benefits, risks, and alternative options of radical cystectomy; or deemed unsuitable for radical cystectomy by the investigator; 8. Subjects of childbearing potential and their partners must use effective contraception measures during the trial and for at least 12 weeks after the last dose. Female subjects of childbearing potential who are not surgically sterilized must have a negative serum HCG test within 7 days before the first dose and must not be breastfeeding;
Exclusion criteria
Exclusion criteria: 1. Subjects with known hypersensitivity to any component of the investigational product; 2. Received surgical treatment or radiotherapy targeting bladder lesions within 2 weeks before first dose; 3. Laboratory tests at screening meeting any of the following criteria: (1) Hematology: Absolute neutrophil count 1.5× upper limit of normal (ULN) or creatinine clearance >= 60 mL/min (calculated by Cockcroft-Gault formula); (3) Hepatic function (no hepatoprotective treatment history within 7 days prior to screening tests): Alanine aminotransferase (AST) > 2.5× ULN; Aspartate aminotransferase > 2.5 × ULN; Total bilirubin (TBIL) > 1.5× ULN; (4) Electrocardiogram: Fridericia-corrected QT interval (QTcF) > 450 ms in males, QTcF > 470 ms in females; (5) Coagulation function: Activated partial thromboplastin time (APTT) > 1.5 × ULN; International normalized ratio (INR) > 1.5 × ULN; Prothrombin time (PT) > 1.5 × ULN; 4. History or evidence of muscle-invasive, locally advanced, metastatic, and/or extravesical bladder cancer (including prostatic urethra); 5. Contraindications to urinary tract and/or cystoscopy, such as urethral stricture, urinary tract infection (UTI) (referring to symptomatic infection with positive urine culture), gross hematuria, small bladder capacity, etc.; 6. Bladder dysfunction at screening, such as severe urinary incontinence or overactive bladder (OAB); Bladder perforation detected by cystoscopy or imaging at screening; 7. Upper urinary tract tumor detected by upper urinary tract examination at screening or prostatic urethral tumor detected by cystoscopy, or concurrent other malignant tumors within 5 years before first dose, except for skin basal cell carcinoma, skin squamous cell carcinoma, cervical carcinoma in situ that have been completely resolved/controlled after treatment, adequately treated stage I/II cancers, or stable prostate cancer under complete remission with active surveillance or well-controlled with androgen therapy; 8. Symptomatic congestive heart failure, New York Heart Association (NYHA) class III or IV heart failure, or other severe cardiac dysfunction deemed clinically significant by the investigator; 9. Severe/unstable angina or myocardial infarction within 6 months prior to screening; 10. History of uncontrolled central nervous system disease; 11. Medical history or examination suggesting active tuberculosis within 1 year before first dose; 12. Severe infection requiring control with antibiotics, antiviral, or antifungal agents; 13. History of immunodeficiency, including HIV seropositivity, other acquired or congenital immunodeficiency diseases; 14. Received systemic glucocorticoid therapy within 2 weeks before first dose of investigational product. Exceptions: steroid dose = 500 IU/mL) or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability and safety (including DLT, types, incidence, and severity of adverse events; changes in clinical laboratory parameters, ECG, vital signs, and physical examination);Phase II validity (CRR at the 12th month in Cohort 1 and 2; DFR at the 12th month in cohort 3); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (including Cmax, Tmax, t1/2, AUC0~inf, AUC0~t, CL/F, Vz/F);Pharmacodynamics (including lymphocyte, CD8+ T lymphocyte, NK cell counts; concentrations of cytokines IL-2, IL-4, IL-6, IL-8, IL-10, TNF-a, IFN-?);Immunogenicity (including ADA incidence and titers, Nab incidence);Efficacy (including duration of complete response in BCG-unresponsive CIS patients, CRR at months 3/6/9/12; BCG-unresponsive Ta/T1 DFS, DFR at months 3/6/9/12; time to progression (TTP), time to cystectomy (TTC), RCR at months 3/6/9/12);Progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), time to progression (TTP), time to cystectomy (TTC) (Cohorts 1, 2, 3);Duration of complete response (Cohorts 1, 2);Complete remission rate (Cohorts 1, 2);Disease-free survival (DFS) (Cohort 3);Disease-free response rate (DFR) (Cohort 3); | — |
Countries
China
Contacts
Public ContactWei Qiang, Feng Ping
West China Hospital of Sichuan University
Outcome results
None listed