A Study of TAR-200 in Combination With Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants With BCG-naïve High-risk Non-muscle Invasive Bladder Cancer (HR-NMIBC) (SunRISe-3)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Bladder Cancer

Treatments: Biological: Cetrelimab; Drug: TAR-200; Biological: BCG Vesiculture

Study type: Interventional

Funder types: Industry

Identifiers

NCT05714202

CR109223

17000139BLC3002 (Other Identifier)

2020-004506-64 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to compare event-free survival (EFS) in participants with Bacillus Calmette-Guerin (BCG)-naive high-risk non-muscle invasive bladder cancer (HR-NMIBC), including high-grade papillary Ta, any T1, or carcinoma in situ (CIS), between TAR-200 plus cetrelimab (Group A) and TAR-200 alone (Group C) versus intravesical BCG (Group B).

Full description

Bladder cancer is the tenth most common malignancy worldwide. About 75 percent (%) of bladder cancers are non-muscle invasive at diagnosis with approximately 25% of NMIBC patients have HR, NMIBC. The TAR-200/gemcitabine (JNJ-17000139) product is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine 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 mainstay of treatment for HR-NMIBC is transurethral resection of bladder tumor, followed by intravesical treatment with BCG. In this study metronomic dosing of intravesical gemcitabine, delivered via TAR-200, alone or in combination with cetrelimab will be evaluated and compared against intravesical BCG. The study consists of a Screening phase, Treatment phase, and Follow-up phase. The total duration of the study will be up to 5 years and 2 months. Efficacy, Safety, pharmacokinetics (PK), and biomarkers will be assessed at specific time points during the study.

Enrollment: 1,050 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed initial diagnosis by local pathology (within 90 days of the most recent signed informed consent) of high grade non-muscle invasive bladder cancer (HR-NMIBC) (high-grade Ta, any T1 or carcinoma in-situ [CIS]), in participants who are Bacillus Calmette Guérin (BCG)-naïve
• BCG-naïve (participants who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before date of randomization are eligible)
• All visible papillary disease must be fully resected (absent) prior to date of randomization and documented at baseline cystoscopy. Local urine cytology at screening must be negative or atypical (for high-grade urothelial carcinoma [HGUC]) for patients with papillary only disease (without CIS)
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
• All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade less than (<) 2 prior to date of randomization
• Participants must be willing to undergo all study procedures

Exclusion criteria

• Presence or history of histologically confirmed, muscle invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, greater than and equal to [>=] T2)
• Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder (that is, urethra, ureter, or renal pelvis). Ta/any 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
• Presence of any bladder or urethral anatomic feature (example, urethral stricture) that, in the opinion of the investigator, may prevent the safe insertion, indwelling use, removal of TAR-200 or administration of intravesical BCG. Participants with tumors involving the prostatic urethra in men will be excluded
• A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 milliliters (mL)
• Indwelling catheters are not permitted; however, intermittent catheterization is acceptable

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,050 participants in 3 patient groups

Treatment Group A: TAR-200 + Cetrelimab

Experimental group

Description:

Participants will receive intravesical TAR-200 once every 3 weeks (Q3W) and cetrelimab.

Treatment:

Drug: TAR-200

Biological: Cetrelimab

Treatment Group B: Bacillus Calmette-Guerin (BCG) Vesiculture

Active Comparator group

Description:

Participants will receive intravesical BCG once every week for 6 weeks (induction) and then followed by once every week for 3 weeks starting at Weeks 12, 24, 48, 72, and 96 (maintenance).

Treatment:

Biological: BCG Vesiculture

Treatment Group C: TAR-200 Alone

Experimental group

Description:

Participants will receive intravesical TAR-200 alone once Q3W.

Treatment:

Drug: TAR-200