Cretostimogene for BCG‑unresponsive high‑grade non‑muscle‑invasive bladder cancer

A Single-arm, Open-label, Multicenter Phase II Clinical Study to Evaluate the Efficacy and Safety of Cretostimogene Grenadenorepvec in Patients With BCG-unresponsive High-risk Non-Muscle Invasive Bladder Cancer

This treatment will test cretostimogene plus n‑dodecyl‑β‑D‑maltoside in adults whose high‑grade non‑muscle‑invasive bladder cancer did not respond to BCG (carcinoma in situ with or without Ta/T1 tumors).

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Lepu Biopharma Co., Ltd. (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 14 sites (Beijing, Beijing Municipality and 13 other locations)
• Trial ID: NCT07283835 on ClinicalTrials.gov

What this trial studies

This is an open‑label, single‑arm Phase 2 study giving intravesical cretostimogene together with n‑dodecyl‑β‑D‑maltoside to patients with BCG‑unresponsive high‑risk non‑muscle‑invasive bladder cancer, specifically carcinoma in situ with or without concomitant high‑grade Ta/T1 disease. All visible Ta/T1 tumors are resected and CIS is resected or fulgurated as feasible before treatment. Patients are followed with scheduled cystoscopies, urine cytology, imaging and biopsies as needed to monitor tumor response and safety. The goal is to measure tumor clearance and durability of response after the single treatment regimen.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed BCG‑unresponsive high‑grade non‑muscle‑invasive bladder cancer (CIS with or without Ta/T1), ECOG 0–2, who have had resection/fulguration of Ta/T1 and CIS as feasible and are willing to undergo study procedures are ideal candidates.

Not a fit: Patients with muscle‑invasive or metastatic bladder cancer, those eligible and willing to proceed with immediate radical cystectomy, or those with inadequate organ function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the treatment could clear carcinoma in situ and reduce recurrence, potentially allowing some patients to avoid or delay radical cystectomy.

How similar studies have performed: Similar intravesical gene‑ and oncolytic‑virus therapies (for example, CG0070 and nadofaragene firadenovec) have shown promising responses in BCG‑unresponsive NMIBC, so this approach has precedent though agents and delivery differ.

Eligibility criteria

Inclusion Criteria:

In order to be eligible for participation in this trial, the patient must:

1. Be ≥18 years of age on day of signing informed consent.

   \- Patients must have pathologically confirmed BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without concomitant Ta/T1 papillary disease.
2. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
3. Have all Ta and/or T1 disease resected and all CIS resected or fulgurated, as feasible, prior to study treatment.
4. Demonstrate adequate organ function.
5. Patients must be willing to comply with study mandated cystoscopies, urine cytology, urograms, biopsies, and other procedures (including TURBT or other resection for all Ta/T1 disease) for the duration of the study. Patients who withdraw consent for these procedures will be withdrawn from the trial.
6. Ineligible to receive radical cystectomy or refusal of radical cystectomy according to Investigator assessment.

Exclusion Criteria:

1. Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer.
2. History of urothelial carcinoma in the upper genitourinary tract (kidney, renal collecting system, ureter) or in the prostatic urethra, including urethral CIS, within 24 months prior to enrollment.
3. Has received systemic anti-cancer therapy, including investigational agents.
4. Has had prior systemic treatment (with the exception of checkpoint inhibitor therapy), radiation therapy, or surgery for bladder cancer other than TURBT or bladder biopsies.
5. Has any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolus, uncontrolled hypertension, or uncontrolled congestive heart failure.
6. Cannot tolerate study-related biopsies, IVE administration, or 1-hour bladder hold of Cretostimogene.

Where this trial is running

Beijing, Beijing Municipality and 13 other locations

• Peking University First Hospital (First Clinical Medical School of Peking University) — Beijing, Beijing Municipality, China (Recruiting)
• Chongqing University Cancer Hospital — Chongqing, Chongqing Municipality, China (Recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)
• The Affiliated Drum Tower Hospital of Nanjing University Medical School — Nanjing, Jiangsu, China (Recruiting)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (Recruiting)
• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)
• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)
• The Second Hospital of Tianjin Medical University — Tianjin, Tianjin Municipality, China (Recruiting)
• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Dinɡwei Ye, M.D. — Fudan University
• Study coordinator: Program Director

Conditions Non Muscle Invasive Bladder Cancer; High-grade Ta/ T1 Papillary Disease Bladder Cancer; high-grade Ta papillary disease; high-grade T1 papillary disease; carcinoma in situ; Bacillus-Calmette-Guerin unresponsive