Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 12:59 AM
Ignite Modification Date:
2025-12-25 @ 12:59 AM
NCT ID:
NCT07189793
Brief 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.
Detailed Description:
Rationale and Objectives. A substantial proportion of HR-NMIBC patients are BCG-unresponsive or BCG-intolerant and face early high-grade recurrence and consideration of cystectomy. This trial evaluates whether adding sequential intravesical chemotherapy (gemcitabine followed by mitomycin C in the same visit) to systemic PD-1 blockade (toripalimab) improves outcomes versus toripalimab alone.
Design. Prospective, open-label, randomised (1:1), parallel-group, phase 2 study at multiple centres in China. Treatment continues until recurrence/progression, unacceptable toxicity, withdrawal, or completion of 24 months.
Interventions.
Arm A (Combination): Toripalimab 240 mg IV every 3 weeks (Q3W) up to 24 months plus intravesical GEM→MMC: gemcitabine 1,000 mg retained \~60 min and drained, then mitomycin C 40 mg retained \~60 min; administered weekly for 6 weeks (induction) and then maintenance every 4 weeks (Q4W) up to month 24 if no high-grade recurrence.
Arm B (Monotherapy): Toripalimab 240 mg IV Q3W up to 24 months.
Assessments. Cystoscopy and urine cytology at months 3, 6, 9, 12 and every 3 months thereafter; abdominopelvic/upper-tract CT or MRI every 24 weeks; routine laboratory tests prior to dosing/instillation. (Exploratory tissue/urine/blood sampling may be performed per protocol.)
Primary Endpoints.
CIS cohort: CR rate at month 3 (proportion). 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.
Non-CIS cohort: Median RFS, defined as time from start of treatment to high-grade Ta recurrence, any T1, or new CIS. Recurrence requires cystoscopic suspicion confirmed by histopathology; if cytology becomes positive prior to histologic confirmation, the recurrence date is set at the first positive cytology once recurrence is subsequently confirmed.
Secondary Endpoints.
CIS cohort: CR rates at months 6, 12, 18, and 24; PFS rates at the same landmarks (progression defined as lamina propria invasion from Ta/CIS to T1, progression to ≥T2, or new nodal/distant metastasis); OS at month 24, EOT+6 months, and EOT+12 months; incidence of adverse events (AEs).
Non-CIS cohort: RFS rates at months 6, 12, 18, and 24; high-grade RFS (HG-RFS) rates at the same landmarks (high-grade recurrence defined as Tis or Ta/T1 high-grade, or muscle-invasive disease at TURBT or cystectomy); PFS rates at months 6/12/18/24; OS at month 24, EOT+6 months, and EOT+12 months; AE incidence.
Exploratory Endpoints.
CIS cohort: 3-month CR rate in PD-L1-positive and PD-L1-negative subgroups (per protocol-specified assay and criteria; no prespecified CPS threshold).
Non-CIS cohort: Median RFS in PD-L1-positive and PD-L1-negative subgroups (recurrence definitions as above).
Sample Size and Oversight. Approximately 106 participants will be randomised 1:1. Safety will be monitored throughout; a Data Monitoring Committee oversees participant protection and study conduct.
Study:
NCT07189793
Study Brief:
Protocol Section:
NCT07189793