Urinary Bladder Neoplasms
Conditions
Brief summary
The purpose of this study is to evaluate the overall complete response (CR) rate in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease; and disease-free survival (DFS) in participants treated with TAR-200 alone with papillary disease only (Cohort 4).
Interventions
DRUGTAR-200
TAR-200 will be administered transuretherally.
BIOLOGICALCetrelimab
Cetrelimab will be administered.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of persistent or recurrent high-risk non-muscle invasive bladder cancer (HR-NMIBC), (carcinoma in situ \[CIS\] or tumor in situ \[Tis\]), with or without papillary disease (T1, high-grade Ta) or papillary disease only (high-grade Ta or any T1 and absence of CIS), within 12 months of completion of the last dose of Bacillus Calmette-Guerin (BCG) therapy, in participants who have received adequate BCG. Mixed histology tumors are allowed if urothelial differentiation (transitional cell histology) is predominant. However, the presence of neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible. For participants with lamina propria invasion (T1) on the screening biopsy/ transurethral resection of bladder tumor (TURBT), muscularis propria must be present in order to rule out Muscle Invasive Bladder Cancer (MIBC) * All visible papillary disease must be fully resected (absent) prior to randomization (residual CIS is acceptable for participants eligible for Cohorts 1, 2, and 3 only) and documented in the electronic case report form (eCRF) at screening cystoscopy. For participants with papillary disease only (Cohort 4), local urine cytology at screening must be negative or atypical (for High-Grade Urothelial Carcinoma \[HGUC\]) * Participants must be ineligible for or have elected not to undergo radical cystectomy * BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as a minimum of 5 of 6 full doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or at least 2 of 6 doses of a second induction course * Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
Exclusion criteria
* Presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, T2, T3, T4, and/or Stage IV) * Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/CIS of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to randomization * Received a live virus vaccine within 30 days prior to the initiation of study treatment. Inactivated (non-live or non-replicating) vaccines approved or authorized for emergency use (for example, COVID-19) by local health authorities are allowed * Active hepatitis B or C infection (for example, participants with history of hepatitis C infection but undetectable hepatitis C virus polymerase chain reaction (PCR) test and participants with history of hepatitis B infection with positive hepatitis B surface antigen (HBsAg) antibody and undetectable PCR are allowed) * Prior therapy with an anti-programmed-cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1, 2, and 3: Overall Complete Response (CR) Rate | From date of first dose up to clinical cut-off date 3rd July 2025 (up to 50 months) | Overall CR rate was defined as the percentage of participants who met at least one of the following: negative cystoscopy and negative (including atypical) centrally read urine cytology, or positive cystoscopy with biopsy-proven benign or low-grade non-muscle invasive bladder cancer (NMIBC) and negative (including atypical) centrally read cytology at any time point. |
| Cohort 4: Disease-free Survival (DFS) | From date of first dose up to clinical cut-off date 3rd July 2025 (up to 50 months) | DFS was defined as the time from the date of first dose of study treatment to the time of one of the following events, whichever occurred first: (1) The first recurrence of high-risk disease (high-grade Ta, any T1 or CIS), (2) progression to muscle invasive bladder cancer (MIBC) (T greater than or equal to \[\>=\] 2) or to lymph node (N+) or to distant disease (M+), whichever occurred first, (3) Death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Laboratory Abnormalities by Severity Grades | From Week 0 up to 6 years 7 months | — |
| Time to Symptom Deterioration as Assessed by European Organisation for Research and Treatment of Cancer Qualityof-life Questionnaire (EORTC QLQ) -C30 Scores | From Week 0 up to 6 years 7 months | — |
| Cohorts 1, 2, and 3: Number of Participants With at Least 12 Months Duration of Response | From onset of first CR up to clinical cut-off date 3rd July 2025 (up to 47.3 months) | DOR was defined as the date of first complete response (CR) achieved to the date of first evidence of recurrence or progression or death, using cystoscopy, centrally read bladder biopsy and urine cytology, and imaging, if available. Complete response was defined as having a negative cystoscopy and negative (including atypical) centrally assessed urine cytology, or positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative (including atypical) centrally assessed cytology at any time point. Number of participants with at least 12 months duration of response were reported. |
| Overall Survival (OS) | From Week 0 up to 6 years 7 months | — |
| Cohorts 1, 2, and 4: Plasma Concentrations of Gemcitabine and 2',2' Difluorodeoxyuridine (dFdU) (Metabolite) | Predose at Week 0 and at any time between Days 2-7 during Weeks 3, 6, 9, 15, 18, and 21 postdose | Plasma concentrations of gemcitabine and dFdU were reported. |
| Cohorts 1 and 2: Maximum Observed Urine Concentration (Cmax) of Gemcitabine and dFdU (Metabolite) | At Week 0 | Cmax was defined as maximum observed urine concentration. |
| Cohort 4: Urine Concentration of Gemcitabine and dFdU (Metabolite) | At Weeks 3, 6, 9, 15, 18, and 21 | Urine concentrations of gemcitabine and dFdU were reported. |
| Cohort 1and 3: Serum Concentration of Cetrelimab | At Weeks 0, 3, 12, 24, 48, 60, 84 (end of infusion) [EOI] | Serum concentration of cetrelimab were reported. |
| Cohort 3: Serum Concentration of Cetrelimab | At Weeks 60 (EOI) | Serum concentration of cetrelimab were reported. |
| Cohorts 1 and 3: Number of Participants With Anti-cetrelimab Antibodies | From date of first dose up to clinical cut-off date 3rd July 2025 (54 months) | Number of participants positive to anti-cetrelimab antibodies was reported using validated immunoassay for anti-drug antibody (ADA) analysis. |
| Change From Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores | From Week 0 up to 6 years 7 months | — |
| Time to Symptom Deterioration as Assessed by EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores | From Week 0 up to 6 years 7 months | — |
| Change From Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores | From Week 0 up to 6 years 7 months | — |
| Number of Participants With Adverse Events (AEs) by Severity Grades | From Week 0 up to 6 years 7 months | — |
Countries
Australia, Belgium, Canada, France, Germany, Greece, Italy, Japan, Netherlands, Portugal, Russia, South Korea, Spain, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
Participants with high-risk non-muscle invasive bladder cancer (NMIBC) and carcinoma in situ (CIS with or without papillary or papillary only) unresponsive to intravesical bacillus Calmette-Guérin (BCG) who were ineligible for or elected not to undergo radical cystectomy were enrolled in the study. Results are currently reported up to primary completion date 03-Jul-25. Remaining results will be posted upon study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 166 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants |
| Age, Continuous | 70.2 years STANDARD_DEVIATION 9.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 204 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 191 Participants |
| Region of Enrollment AUSTRALIA | 2 Participants |
| Region of Enrollment BELGIUM | 9 Participants |
| Region of Enrollment CANADA | 3 Participants |
| Region of Enrollment FRANCE | 9 Participants |
| Region of Enrollment GERMANY | 18 Participants |
| Region of Enrollment GREECE | 4 Participants |
| Region of Enrollment ITALY | 9 Participants |
| Region of Enrollment JAPAN | 2 Participants |
| Region of Enrollment NETHERLANDS | 8 Participants |
| Region of Enrollment PORTUGAL | 2 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 0 Participants |
| Region of Enrollment SOUTH KOREA | 16 Participants |
| Region of Enrollment SPAIN | 13 Participants |
| Region of Enrollment UNITED STATES | 12 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 53 | 7 / 85 | 0 / 28 | 2 / 52 |
| other Total, other adverse events | 51 / 53 | 78 / 85 | 22 / 28 | 44 / 52 |
| serious Total, serious adverse events | 17 / 53 | 22 / 85 | 3 / 28 | 10 / 52 |
Outcome results
None listed