Urinary Bladder Neoplasms
Conditions
Brief summary
The purpose of this study is to evaluate the anti-tumor effects of TAR-200 in combination with intravenous (IV) cetrelimab and IV cetrelimab alone.
Detailed description
Bladder cancer is the tenth most common malignancy worldwide. Approximately 25 percent (%) of all new bladder cancer participants present with muscle invasive bladder cancer (MIBC) at the time of diagnosis, and roughly 50% will ultimately develop distant metastases. The TAR-200/ gemcitabine (JNJ-17000139) product is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine minitablets and osmotic minitablets. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds programmed-cell death protein (PD)-1. The standard of care in MIBC includes radical cystectomy (RC) with urinary diversion and is considered the preferred treatment option for participants who are considered surgical candidates. Study consists of a Screening phase, Treatment phase and follow-up phase. The total duration of study will be up to 2 years and 6 months. Efficacy, safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time points during this study.
Interventions
DRUGTAR-200
TAR-200 will be administered.
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 proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes are allowed if tumor(s) demonstrate urothelial predominance. However, the presence of small cell or neuroendocrine variants will make a participant ineligible * Participants with no residual tumor, or intravesical tumor size of less than or equal to (\<=)3 centimeter (cm) following transurethral resection of bladder tumor (TURBT) are eligible; debulking TURBT for any residual disease is encouraged but not mandated. Participants with persistent tumors greater than (\>)3 cm at screening must undergo a second debulking, re-staging TURBT. Participants will be ineligible if any individual tumor is \>3 cm after debulking TURBT * Deemed eligible for and willing to undergo RC by the operating urologist * Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1 * Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal tests results * All adverse events associated with any prior surgery must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade less than (\<) 2 prior to randomization
Exclusion criteria
* Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment * Participants must not have evidence of cT4b, or N1-3, or M1 disease based on central radiology staging (chest, abdomen, and pelvis must be performed using computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) within 42 days prior to randomization * Presence of any bladder or urethral anatomic feature that, in the opinion of the Investigator, may prevent the safe placement, indwelling use, or removal of TAR-200 * Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time * Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to enrollment * Participants with evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has resolved prior to dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) Rate | At Week 12 | pCR was defined as percentage of participants who achieved complete pathologic response. Complete pathologic response is defined as ypT0N0 (no evidence of disease) as assessed by pathologic evaluation on radical cystectomy (RC) specimen. pCR was determined by central pathologic review. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment Emergent Adverse Event According to Common Terminology Criteria for Adverse Event (CTCAE) Version 5 Grades | Cycle Day 1 up to Week 124 |
| Number of Participants With Worst Post-baseline Laboratory Values Based on Common Terminology Criteria for Adverse Events (CTCAE) | Cycle Day 1 up to Week 124 |
| Recurrence-Free Survival (RFS) | Cycle Day 1 up to Week 124 |
Countries
Belgium, France, Germany, Israel, Italy, Netherlands, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Pre-assignment details
Participants with muscle-invasive urothelial carcinoma of the bladder (MIBC) who were scheduled for radical cystectomy (RC) and were ineligible for or refusing cis-platinum based neoadjuvant chemotherapy were enrolled in the study. Results are currently reported up to cut off date that is 09 May 2025. Remaining results will be posted upon study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical 85 years and over | 0 Participants |
| Age, Categorical Adults (18-64 years) | 15 Participants |
| Age, Categorical From 65 to 74 years | 31 Participants |
| Age, Categorical From 75 to 84 years | 44 Participants |
| Age, Continuous | 67.7 years STANDARD_DEVIATION 8.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 118 Participants |
| Region of Enrollment Belgium | 17 Participants |
| Region of Enrollment France | 6 Participants |
| Region of Enrollment Germany | 2 Participants |
| Region of Enrollment Israel | 1 Participants |
| Region of Enrollment Italy | 4 Participants |
| Region of Enrollment Korea, South | 12 Participants |
| Region of Enrollment Spain | 28 Participants |
| Region of Enrollment United Kingdom | 2 Participants |
| Region of Enrollment United States | 42 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 14 / 104 | 8 / 59 |
| other Total, other adverse events | 95 / 101 | 53 / 58 |
| serious Total, serious adverse events | 60 / 101 | 26 / 58 |
Outcome results
None listed