First Affiliated Hospital of Wenzhou Medical University
Phase
Phase 2
Started
2026-12
Last updated
2026-09-08
Condition(s) studied
Urinary Bladder NeoplasmsCarcinoma, Transitional CellCarcinoma in Situ of BladderNon-Muscle-Invasive Bladder Cancer
Investigational drug(s) / intervention(s)
ToripalimabGemcitabine (GEM)Mitomycin C (MMC)
Toripalimab: PD-1 inhibitor administered intravenously every 3 weeks (Q3W) for up to 24 months. Starts during the first intravesical treatment cycle.
Gemcitabine (GEM): Intravesical instillation as part of a sequential regimen with mitomycin C: weekly for 6 weeks (induction); if no recurrence at first tumour assessment (\~month 3), maintenance instillations continue monthly up to 24 months.
Mitomycin C (MMC): Intravesical instillation immediately after intravesical gemcitabine in the same visit (sequential regimen): weekly for 6 weeks (induction); if eligible, monthly maintenance up to 24 months.
Study summary
This open-label, randomised, multicentre, phase 2 study (OHAI-NMIBC-01) compares toripalimab plus sequential intravesical gemcitabine followed by mitomycin C (GEM→MMC) with toripalimab alone in adults with BCG-unresponsive or BCG-intolerant high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Two prespecified cohorts are analysed: (1) CIS cohort (CIS with/without Ta/T1) and (2) non-CIS cohort (high-risk Ta/T1 without CIS). In the combination arm, intravesical GEM→MMC is given weekly for 6 weeks (induction) and, for patients without recurrence at the first tumour assessment (\~month 3), monthly maintenance continues up to 24 months or until progression/unacceptable toxicity; toripalimab IV every 3 weeks starts during the first intravesical cycle and continues up to 24 months or until progression/unacceptable toxicity. The monotherapy arm receives toripalimab IV every 3 weeks up to 24 months or until progression/unacceptable toxicity. Cystoscopy and urine cytology are performed every 3 months; imaging every 24 weeks. Primary endpoints are 3-month complete response (CR) rate in the CIS cohort and median recurrence-free survival (RFS) in the non-CIS cohort. Secondary endpoints include landmark CR, PFS and OS, RFS/HG-RFS landmarks in the non-CIS cohort, and safety (CTCAE v5.0). Exploratory analyses will assess outcomes by protocol-defined PD-L1 status. Approximately 106 participants will be enrolled at multiple sites in China.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Age ≥18 years; sex: all; signed written informed consent by the participant or legally authorised representative.
2. Histologically confirmed high-risk non-muscle-invasive bladder cancer (HR-NMIBC), defined as any T1, high-grade Ta, and/or carcinoma in situ (CIS).
3. BCG-intolerant (unable to continue BCG because of severe adverse reactions) or meeting at least one definition of BCG treatment failure:
1. Persistent or recurrent CIS within 12 months after completion of adequate BCG (with or without concomitant NMIBC);
2. Recurrent high-grade Ta/T1 within 6 months after completion of adequate BCG;
3. High-grade T1 at the first evaluation after BCG induction (\~3 months);
4. Ta high-grade and/or CIS present or recurrent at \~3 months after receiving ≥5 BCG instillations.
Adequate BCG, for the purposes of this protocol, is defined as receipt of at least 5 of 6 induction instillations (maintenance not required).
4. ECOG performance status 0-2.
5. Adequate organ function per protocol laboratory criteria.
6. No intravesical chemotherapy or immunotherapy between the most recent cystoscopy/TURBT and study start; a single immediate postoperative intravesical chemotherapy at the time of the most recent cystoscopy/TURBT is allowed during screening per local practice.
7. Willing and able to comply with study procedures.
Exclusion Criteria:
1. Muscle-invasive bladder cancer (T2-T4).
2. Low-grade (LG) recurrence during or after BCG therapy.
3. Concomitant upper tract urothelial carcinoma, or lymph-node/distant metastasis.
4. Indwelling ureteral stent or known vesicoureteral reflux.
5. Contraindications to intravesical instillation, including within 2 weeks after TURBT, bladder perforation, symptomatic urinary tract infection, or gross haematuria.
6. Known hypersensitivity or contraindication to gemcitabine, mitomycin C, or toripalimab.
7. Systemic chemotherapy, small-molecule targeted therapy, or radiotherapy within 2 weeks before first study treatment.
8. Prior immune checkpoint inhibitor therapy.
9. Pregnant, planning pregnancy, or breastfeeding women.
10. Ongoing acute or chronic systemic infection, or history of active tuberculosis.
11. Other malignancy requiring active treatment.
12. Any condition that, in the investigator's judgment, makes participation not in the patient's best interest or could confound study results.
Study Population Adults with BCG-unresponsive or BCG-intolerant HR-NMIBC treated at participating centres in China.
Primary outcome measure(s)
Complete Response (CR) Rate at Month 3 in the CIS Cohort — Baseline to Month 3 Proportion of participants in the CIS cohort achieving CR at month 3. CR is met by any of the following protocol-specified scenarios indicating no high-grade bladder disease: (a) negative urine cytology and negative cystoscopy; (b) negative cytology with cystoscopic lesions that are benign or low-grade Ta on biopsy; or (c) negative cystoscopy with positive cytology attributed to tumour in the upper tract or prostatic urethra and random bladder biopsies negative.
Median Recurrence-Free Survival (RFS) in the Non-CIS Cohort — From randomisation/start of treatment to first event, assessed up to 24 months RFS is time to high-grade Ta recurrence, any T1, or new CIS, whichever occurs first. Recurrence requires cystoscopic suspicion confirmed by histopathology; if cytology becomes positive before histologic confirmation, the recurrence date is set at the first positive cytology once recurrence is subsequently confirmed. Death from any cause before documented recurrence is counted as an event.
Trial sites (1)
Facility
City
Region
Status
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou
Zhejiang
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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