Non-muscle-invasive bladder cancer
Conditions
Interventions
Experimental Group A(1µg,4ug):Accelerated titration, PTT-936 bladder perfusion
Experimental Group B(10µg,20µg,35µg,50µg0:3+3 design, dose escalation, PTT-936 bladder perfusion
Experimental Group C(An additional 3 to 9 subjects will be enrolled in one or more (expected no more than 3) dose groups that have been determined to be safe):Expanded enrollment, PTT-936 bladder perf
Sponsors
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign the Informed Consent Form (ICF); 2. Able and willing to comply with all study procedures; 3. Male or female subjects aged >=18 years at the time of signing the ICF; 4. BMI >=18 kg/m^2. 5. Subjects must have tumor disease meeting the following criteria: (1) Patients with histologically confirmed high-risk non-muscle invasive bladder cancer (NMIBC) [as defined by the 2025 CSCO guidelines: high-risk defined as Grade 3 (high-grade) tumor meeting any of the following: CIS; T1 stage; tumor diameter >3 cm; multiple tumors, recurrent tumors, meeting high-risk definition], based on biopsy results obtained within 8 weeks prior to the first dose of study treatment. If multiple bladder biopsies are required to confirm eligibility, the last bladder biopsy must be performed within 8 weeks prior to the first dose; Patients meeting criterion 5.1 must have BCG-unresponsive disease, or be intolerant to BCG, or have BCG unavailable, or refuse BCG and have relapsed after failed intravesical chemotherapy. (2) Patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC) as defined by the 2025 CSCO guidelines: all tumors not included in the definitions of adjacent categories (i.e., between low-risk and high-risk). [Low-risk is defined as papillary urothelial neoplasm of low malignant potential, or meeting all of the following: solitary, low-grade, Ta stage, diameter =3 cm. High-risk is defined as Grade 3 (high-grade) tumor meeting any of the following: CIS; T1 stage; diameter >3 cm; multiple tumors, recurrent tumors, meeting high-risk definition.] 6. Ta or T1 tumors must have been resected by TURBT within 12 weeks prior to the start of study treatment; for patients with high-risk/very high-risk NMIBC with T1 lesions, a restaging TURBT must be performed within 6 weeks after the initial TURBT (the restaging TURBT must be performed within 8 weeks prior to the start of study treatment). 7. Within 21 days prior to the first dose, no visible papillary tumors on cystoscopy and negative urine cytology (except for patients with CIS); if TURBT is performed within 21 days prior to the first dose, repeat cystoscopy is not required; 8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0–1; 9. Adequate end-organ and hematopoietic function (as defined by the following laboratory results obtained within 7 days prior to the first dose): 10. For women of childbearing potential (WOCBP, Appendix 4): must agree to remain completely abstinent or use at least one acceptable method of contraception from screening until 3 months after the last dose of study drug. Acceptable methods of contraception are those that, alone or in combination, have a low failure rate (i.e., 6 months prior to the first dose are exempt from this criterion.
Exclusion criteria
Exclusion criteria: 1. Current or past history of muscle-invasive (Stage T2 or higher) or locally advanced (T3/T4, any N) or metastatic bladder cancer; 2. History of urothelial carcinoma of the upper genitourinary tract (kidney, renal collecting system, ureter) or prostatic urethra (including urethral CIS) within 24 months prior to enrollment; 3. Prior systemic therapy for bladder cancer, bladder radiotherapy, or bladder cancer surgery other than TURBT or bladder biopsy; 4. Inability to tolerate study-related biopsy or intravesical administration of study drug; 5. Received intravesical adjuvant therapy for bladder cancer within 8 weeks prior to the start of study treatment for patients with high-risk NMIBC; 6. Received systemic corticosteroids or other immunosuppressive therapy for any indication within 14 days prior to the first dose; 7. Prior history of organ transplantation or allogeneic hematopoietic stem cell transplantation; 8. Active hepatitis B with positive HBsAg; 9. Positive for human immunodeficiency virus (HIV); 10. Positive test for hepatitis C virus (HCV) antibody, unless HCV ribonucleic acid (RNA) testing shows HCV viral load below the lower limit of reference; 11. Active syphilis (positive specific antibody test (TPPA/TPHA) with elevated non-specific antibody test titers (e.g., RPR/TRUST)); 12. Presence of a disease or metabolic dysfunction, physical examination finding, or clinical laboratory abnormality that provides reasonable suspicion of a disease or condition that would contraindicate the use of study treatment or limit compliance with study requirements; 13. Received a live vaccine within 30 days prior to signing the ICF; 14. Current ocular disease requiring interventional treatment, such as conjunctivitis, keratitis, or fundus disease; 15. Active systemic autoimmune disease or history of a potentially relapsing autoimmune disease; 16. Major trauma or major surgery within 4 weeks prior to signing the ICF, or anticipated need for major surgery during participation in the study. Presence of a serious, non-healing wound, ulcer, or bone fracture; 17. History or current presence of any of the following cardiovascular or cerebrovascular events or diseases: (1) Myocardial infarction, unstable or severe angina pectoris, or arterial thrombotic event within 12 months prior to signing the ICF; (2) Significant abnormality on ECG at screening; (3) Current New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF); (4) Left ventricular ejection fraction (LVEF) <50%; (5) Other cardiac disease considered clinically significant by the investigator; (6) Poorly controlled hypertension despite appropriate antihypertensive therapy, or poor compliance with antihypertensive treatment regimen; 18. Clinically significant third-space fluid accumulation within 3 months prior to the first dose; 19. Active bleeding disorder or recent history (within the past 6 months) of such a disorder; 20. Active thrombophlebitis or thromboembolism not adequately controlled with anticoagulant therapy; 21. Poorly controlled diabetes mellitus; 22. Chronic severe liver disease (hepatic encephalopathy, hepatorenal syndrome, etc.) or Child-Pugh Class B or higher in patients with liver cirrhosis; 23. Any active or symptomatic bacterial, viral, or fungal infection requiring systemic therapy within 14 days prior to the first dose (7 days for urinary tract infection). Prophylactic antimicrobial therapy per institutional protocols is acceptable;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicities (DLTs) and overall safety profile of PTT-936 for injection;Incidence of TEAEs and TRAEs (severity determined using NCI CTCAE v6.0), >= Grade 3 TEAEs, >= Grade 3 TRAEs, SAEs, and AESIs;Clinically significant laboratory abnormalities/changes from baseline in safety laboratory results assessed according to NCI CTCAE v6.0;Clinically significant abnormal ECG, vital signs, and physical examination findings/changes from baseline;The recommended Phase II dose (RP2D) of PTT-936 for injection will be determined based on safety, tolerability, and changes in serum and urine cytokines; | — |
Secondary
| Measure | Time frame |
|---|---|
| For high-risk NMIBC with CIS lesions: complete response rate (CRR) and duration of response (DOR) at 3 and 6 months;For high-risk NMIBC without CIS lesions at baseline: recurrence-free survival (RFS) rate at 6 and 12 months;For intermediate-risk NMIBC: recurrence-free survival time or RFS;Pharmacokinetic parameters of PTT-936 and PTT-938 at specified time points (including AUC, Cmax, Cmin, CL/F, V/F, and t1/2); | — |
Countries
China
Contacts
Public ContactTianxin Lin
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Outcome results
None listed