A Phase 2 interventional study of Toripalimab and Gemcitabine (GEM) in Urinary Bladder Neoplasms, Carcinoma, Transitional Cell and Carcinoma in Situ of Bladder, sponsored by First Affiliated Hospital of Wenzhou Medical University. Not yet recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-08.
Sponsored by First Affiliated Hospital of Wenzhou Medical University · Phase 2, Interventional, and Treatment
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.
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.
294 studies on the registry are indexed under Non-Muscle Invasive Bladder Neoplasms; 126 are open to participants now.
This study's planned enrollment of 106 is above the median of 62 across 231 interventional studies indexed under Non-Muscle Invasive Bladder Neoplasms.
Browse Non-Muscle Invasive Bladder Neoplasms studies →First Affiliated Hospital of Wenzhou Medical University is the lead sponsor of 83 studies on the registry; 57 are open to participants now.
Compared within Non-Muscle Invasive Bladder Neoplasms, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Urinary Bladder Neoplasms. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
BCG-intolerant (unable to continue BCG because of severe adverse reactions) or meeting at least one definition of BCG treatment failure:
Adequate BCG, for the purposes of this protocol, is defined as receipt of at least 5 of 6 induction instillations (maintenance not required).
Exclusion Criteria:
Study Population Adults with BCG-unresponsive or BCG-intolerant HR-NMIBC treated at participating centres in China.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Toripalimab IV Q3W starting with the first intravesical cycle, plus sequential intravesical gemcitabine followed by mitomycin C in the same visit. Induction weekly ×6; if no recurrence at first tumour assessment (\~month 3), monthly maintenance up to 24 months.
Drug: Toripalimab · Drug: Gemcitabine (GEM) · Drug: Mitomycin C (MMC)
Toripalimab IV every 3 weeks (Q3W) up to 24 months or until disease progression, unacceptable toxicity, or withdrawal; no intravesical chemotherapy.
Drug: Toripalimab
PD-1 inhibitor administered intravenously every 3 weeks (Q3W) for up to 24 months. Starts during the first intravesical treatment cycle.
Also known as: JS001, Tuoyi
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.
Also known as: GEM
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.
Complete Response (CR) Rate at Month 3 in the CIS Cohort
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.
Time frame: Baseline to Month 3
Median Recurrence-Free Survival (RFS) in the Non-CIS Cohort
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.
Time frame: From randomisation/start of treatment to first event, assessed up to 24 months
CR Rates at Months 6, 12, 18, and 24 in the CIS Cohort
Proportion of participants in the CIS cohort with CR at the specified time points using the protocol CR definition.
Time frame: Baseline to months 6, 12, 18, and 24
Progression-Free Survival (PFS) Rates at Months 6, 12, 18, and 24 in the CIS Cohort
Proportion without progression at each time point. Progression is defined as lamina propria invasion from Ta/CIS to T1, or progression to ≥T2, or new nodal or distant metastasis.
Time frame: Baseline to months 6, 12, 18, and 24
Overall Survival at Month 24, EOT+6 Months, and EOT+12 Months in the CIS Cohort
Survival status at prespecified landmarks.
Time frame: Baseline to Month 24, EOT+6 months, and EOT+12 months
Incidence of Adverse Events in the CIS Cohort
Participants with treatment-emergent AEs and grade ≥3 AEs (MedDRA; CTCAE v5.0). Immune-related and instillation-related events summarised.
Time frame: From first dose/instillation to 90 days post-last dose/instillation (≈ up to 27 months)
Recurrence-Free Survival Rates at Months 6, 12, 18, and 24 in the Non-CIS Cohort
Proportion without recurrence (high-grade Ta, any T1, or new CIS) or death at each time point; recurrence confirmation rules per protocol.
Time frame: Baseline to months 6, 12, 18, and 24
High-Grade Recurrence-Free Survival (HG-RFS) Rates at Months 6, 12, 18, and 24 in the Non-CIS Cohort
Proportion without high-grade recurrence at each time point. High-grade recurrence is defined as Tis or Ta/T1 high-grade, or muscle-invasive disease identified at TURBT or cystectomy.
Time frame: Baseline to months 6, 12, 18, and 24
Progression-Free Survival Rates at Months 6, 12, 18, and 24 in the Non-CIS Cohort
Proportion without progression (lamina propria invasion from Ta/CIS to T1, progression to ≥T2, or new nodal/distant metastasis). Death before documented progression counts as an event.
Time frame: Baseline to Months 6, 12, 18, and 24
Overall Survival at Month 24, EOT+6 Months, and EOT+12 Months in the Non-CIS Cohort
Survival status at prespecified landmarks.
Time frame: Baseline to Month 24, EOT+6 months, and EOT+12 months
Incidence of Adverse Events in the Non-CIS Cohort
Participants with treatment-emergent AEs and grade ≥3 AEs (MedDRA; CTCAE v5.0).
Time frame: From first dose/instillation to 90 days post-last dose/instillation (≈ up to 27 months)
CR Rate at Month 3 in PD-L1-Positive Participants in the CIS Cohort
Proportion of PD-L1-positive participants in the CIS cohort who achieve CR at Month 3. CR is met by any of: (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.
Time frame: Baseline to Month 3
CR Rate at Month 3 in PD-L1-Negative Participants in the CIS Cohort
Proportion of PD-L1-negative participants in the CIS cohort who achieve CR at Month 3; CR definition as above.
Time frame: Baseline to Month 3
Median Recurrence-Free Survival in PD-L1-Positive Participants in the Non-CIS Cohort
RFS is time from randomisation/start of treatment 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 event date is the first positive cytology once recurrence is subsequently confirmed. Death before recurrence counts as an event.
Time frame: From randomisation/start of treatment to first event, up to 24 months
Median Recurrence-Free Survival in PD-L1-Negative Participants in the Non-CIS Cohort
RFS definition and event-dating rules as above.
Time frame: From randomisation/start of treatment to first event, up to 24 months
Plan to share: Undecided — The sponsor and investigators intend to share de-identified IPD but the final plan (scope, timing, and access mechanism) is pending institutional approvals. This record will be updated once the IPD sharing policy is finalised.
Start is estimated for Dec 2026; primary completion for Oct 2027, 10 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Gemcitabine · Mitomycin
Non-Muscle Invasive Bladder Neoplasms →
First Affiliated Hospital of Wenzhou Medical University