Toripalimab plus BCG bladder instillation after TURBT for high‑risk non‑muscle‑invasive bladder cancer

A Prospective, Open-label, Single-center Clinical Study Evaluating the Efficacy and Safety of Trastuzumab Combined With BCG Perfusion as an Adjuvant Treatment After TURBT in High-risk/Very High-risk Non-muscle-invasive Bladder Cancer

This trial will test whether adding toripalimab (a PD‑1 immunotherapy) to BCG bladder instillations after TURBT helps people with high‑risk or very high‑risk non‑muscle‑invasive bladder cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Changhai Hospital (Academic / other)
• Drugs / interventions: toripalimab, chemotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07307456 on ClinicalTrials.gov

What this trial studies

This is a single‑center, open‑label, non‑randomized Phase 2 study at Changhai Hospital enrolling adults with high‑risk or very high‑risk NMIBC after TURBT. Participants will receive systemic toripalimab combined with intravesical BCG instillations as adjuvant therapy and will be followed for safety and cancer control outcomes. The study is planned from December 2025 through December 2028 under principal investigators from the Department of Urology. The primary focus is on tolerability and preliminary effectiveness of the combination to reduce recurrence and avoid radical cystectomy.

Who should consider this trial

Good fit: Adults aged 18–75 with a pathological diagnosis of high‑risk or very high‑risk non‑muscle‑invasive bladder cancer after TURBT are the intended participants.

Not a fit: Patients with muscle‑invasive or metastatic bladder cancer, those ineligible for systemic immunotherapy, or those unable to travel to the single study site in Shanghai are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could offer a bladder‑sparing treatment option that lowers recurrence risk for patients who otherwise face radical cystectomy.

How similar studies have performed: Other PD‑1 inhibitors (for example, pembrolizumab) have shown activity in BCG‑unresponsive NMIBC and combining systemic immunotherapy with intravesical BCG is an emerging approach with encouraging early signals but is not yet standard of care.

Eligibility criteria

Inclusion Criteria:

1. Age 18-75 years.
2. Patients with a pathological diagnosis of high-risk or very high-risk non-muscle-invasive bladder cancer (NMIBC) following transurethral resection or cystoscopic biopsy.

"High-risk patients" must meet any one of the following criteria:

1. All T1 high-grade (HG)/G3 without carcinoma in situ (CIS), excluding those in the very high-risk group.
2. All CIS patients, excluding those in the very high-risk group.
3. Ta low-grade (LG)/G2 or T1 G1 without CIS, accompanied by three risk factors.
4. Ta HG/G3 or T1 LG without CIS, accompanied by at least two risk factors.
5. T1 G2 without CIS, accompanied by at least one risk factor. "Very high-risk patients" must meet any one of the following criteria:

(1) Ta HG/G3 with CIS accompanied by three risk factors. (2) T1 G2 with CIS accompanied by at least two risk factors. (3) T1 HG/G3 with CIS accompanied by at least one risk factor. (4) T1 HG/G3 without CIS, accompanied by three risk factors. (Risk factors: age \>70 years; tumor diameter \>3 cm; multiple papillary carcinomas) 3. No prior treatment with therapies targeting PD-1, PD-L1, PD-L2, or CTLA-4, or other antibodies or drugs specifically targeting T-cell co-stimulation or checkpoint pathways (immune checkpoint blockers), or bacille Calmette-Guérin (BCG) therapy.

4\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Adequate organ function, defined as meeting the following criteria (within 14 days prior to enrollment, without transfusion or granulocyte colony-stimulating factor treatment): "Hematology": i. Absolute neutrophil count (ANC) ≥1,000/mm³ ii. Platelet count ≥75,000/mm³ iii. Hemoglobin ≥8.0 g/dL "Hepatic function": i. Total bilirubin ≤1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin \>1.5 × ULN.

ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN.

"Renal function": Creatinine clearance (CrCl) \>30 mL/min, calculated using the Cockcroft-Gault formula.

6\. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to enrollment, be willing to use effective contraception during the study period and for at least 6 months after the last dose of study drug (including chemotherapy agents and toripalimab). Male subjects with female partners of childbearing potential must agree to use effective contraception during the study period and for at least 6 months after the last dose.

7\. Subjects voluntarily agree to participate in the study by providing written informed consent, demonstrate good compliance, and are willing to cooperate with follow-up.

Exclusion Criteria:

Patients meeting any of the following criteria were excluded from this study:

1. History or presence of muscle-invasive or disseminated/metastatic bladder cancer. Patients with locally advanced or metastatic bladder cancer or concurrent upper tract urothelial carcinoma were excluded.
2. Prior surgical intervention for bladder cancer other than transurethral resection of bladder tumor (TURBT) and/or bladder biopsy.
3. Administration of any other approved systemic anticancer therapy or systemic immunomodulatory agents (including, but not limited to, interferon, interleukin-2, and tumor necrosis factor) within 28 days prior to enrollment.
4. Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to enrollment.
5. Major surgery or significant trauma within 28 days prior to enrollment.
6. Vaccination with a live vaccine within 28 days prior to enrollment.
7. Use of any Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days prior to enrollment.
8. Treatment with systemic corticosteroids within 4 weeks prior to the study intervention.
9. Active autoimmune diseases requiring systemic treatment or other conditions necessitating long-term use of high-dose corticosteroids and other immunosuppressive agents.
10. History of potassium, sodium, or calcium abnormalities, hypoalbuminemia, interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases (including diabetes, hypertension, cardiovascular diseases, etc.) that, in the investigator's judgment, could affect the treatment.
11. Active viral hepatitis B or C. Patients with acute or chronic active hepatitis B or C infection were excluded if they met any of the following criteria: hepatitis B virus (HBV) DNA \>2000 IU/mL or 10⁴ copies/mL; hepatitis C virus (HCV) RNA \>10³ copies/mL; or co-positivity for hepatitis B surface antigen (HBsAg) and anti-HCV antibody.
12. Known history of human immunodeficiency virus (HIV) infection or known diagnosis of acquired immunodeficiency syndrome (AIDS) (no screening tests were required).
13. History of any organ transplantation, including allogeneic stem cell transplantation, except for transplants not requiring immunosuppression (e.g., corneal transplant, hair transplant).
14. Known history of allergic reactions to any of the study drugs.
15. Concurrent participation in another clinical trial.
16. History and/or concurrent presence of other malignancies, except for: malignancies treated with curative intent with no recurrence for over 3 years, or early-stage cancers considered cured, including completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
17. Active central nervous system metastases or carcinomatous meningitis.
18. Any condition that, in the investigator's opinion, rendered the patient unsuitable for study participation (e.g., treatment not in the patient's best interest, poor patient compliance, etc.).

Where this trial is running

Shanghai, Shanghai Municipality

• ChangHai Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Shuxiong Zeng, Doctor

Conditions Bladder Cancer; HR-NMIBC; Immunotherapy; BCG; Bladder preservation treatment