BCG-naïve High-Risk Non-Muscle Invasive Bladder Cancer MedDRA version: 20.0 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. Age =18 years (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent. Disease Characteristic 2. Criterion modified per Global Amendment 1 2.1 Criterion modified per Global Amendment 2 2.2 Histologically confirmed initial diagnosis by local pathology (within 90 days of the most recent signed informed consent) of HR-NMIBC (high-grade Ta,any T1 or CIS), [AJCC 2017], in participants who are BCG-naïve. 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. Participants may have had a history of HR-NMIBC (defined as high-grade Ta, any T1, or CIS) as long as it has been >3 years from current/novel diagnosis of HR-NMIBC (high-grade Ta, any T1 or CIS). 3. 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) (Kamat 2016). 4. Participants must be willing to undergo all study procedures (eg, multiple cystoscopies from Screening through the end of study and TURBT/bladder biopsy for assessment of recurrence/progression). 5. Criterion modified per Global Amendment 2 5.1 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 HGUC) for patients with papillary only disease (without CIS). 6. All AEs associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE version 5.0 Grade 1.5xULN (except participants with Gilbert’s Syndrome, who must have a total bilirubin 30 mL/min using the Cockcroft-Gault formula. (See Section 10.15: Appendix 15). Sex and Contraceptive/Barrier Requirements For inclusion criteria 10-11 Please see the protocol. Informed Consent 12. Criterion modified per Global Amendment 1 12.1 Participants must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study and agree to store samples when applicable. 13. Participants must be willing and able to adhere to the lifestyle restrictions specified in this protocol. Are the tri
Exclusion criteria
Exclusion criteria: Disease Characteristics 1.Criterion modified per Global Amendment 1 1.1 Presence or history of histologically confirmed, muscle invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (ie, =T2). 2. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder (ie, 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. 3. Criterion modified per Global Amendment 2 3.1 N+ and/or M+ per blinded independent central review (BICR) of computed tomography/magnetic resonance (CT/MR) Urography and chest CT. Any history of HR-NMIBC (high-grade Ta, any T1 or CIS) <3 years from current diagnosis. Medical Conditions 4.1 Active malignancies (ie, progressing or requiring treatment change in the last 24 months prior to randomization) other than the disease being treated under study. Potential allowed exceptions include the following (others may be allowed with Sponsor approval). a. skin cancer (non-melanoma or melanoma) that is considered completely cured. b. non-invasive cervical cancer treated that is considered completely cured. c. adequately treated lobular carcinoma in situ (LCIS) and ductal CIS d. history of localized breast cancer and receiving antihormonal agents e. history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy f. Locerion modified per Global Amendment 2alized prostate cancer (N0M0): i. with a Gleason score of 6, treated within the last 24 months or untreated and under surveillance, ii. with a Gleason score of 3+4 that has been treated more than 6 months prior to full study Screening and considered to have a very low risk of recurrence, iii. or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence. 5. Presence of any bladder or urethral anatomic feature (eg, 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. 6. A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 mL. 7.1 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 (eg,COVID-19) by local health authorities are allowed. 8.1. Participants should not have a history of acute ischemic heart disease within 42 days of randomization, or history of uncontrolled cardiovascular disease including any of the following in the 3 months prior to randomization: a. unstable angina, b. myocardial infarction, c. ventricular fibrillation, d. Torsades de Pointes, e. cardiac arrest, or known congestive New York Heart Association Class III-IV heart failure, f. cerebrovascular accident, g. transient ischemic attack, or h. pulmonary embolism or other venous thromboembolism in the 3 months prior to randomization. 9. Indwelling catheters are not permitted; however, intermittent catheterization is acceptable. 10. Participants must not have clinically significant liver disease that precludes participant treatment regimens prescribed on the study (including, but not limited to active viral, alcoholic, or othe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare event-free survival (EFS) in participants with BCG-naïve HR-NMIBC (high-grade papillary Ta, any T1, or CIS), receiving TAR-200 + IV cetrelimab (Group A) versus intravesical BCG (Group B) and TAR-200 alone (Group C) versus intravesical BCG (Group B).;Secondary Objective: Secondary Objectives - To compare the overall complete response (CR) rate and the duration of CR in participants with BCG naïve CIS receiving TAR-200 + IV cetrelimab (Group A) versus intravesical BCG (Group B) and TAR 200 alone (Group C) versus intravesical BCG (Group B). - To compare recurrence-free survival (RFS) in participants with BCG-naïve HR-NMIBC high-grade papillary Ta or any T1, receiving TAR 200 + IV cetrelimab (Group A) versus intravesical BCG (Group B) and TAR 200 alone (Group C) versus intravesical BCG (Group B). - To compare time to progression (TTP) in participants with BCG-naïve HR NMIBC high-grade papillary Ta or any T1 or CIS receiving TAR 200 + IV cetrelimab (Group A) versus intravesical BCG (Group B) and TAR 200 alone (Group C) versus intravesical BCG (Group B). For the full list of secondary objectives, please refer the protocol. ;Primary end point(s): event-free survival (EFS) EFS will be measured as the time from randomization to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first For participants with CIS, persistent disease at 6 months (Week 24) is also considered an EFS event. Progression is defined as: 1) an increase of stage from Ta to T1 or from CIS to T1, or 2) progression to MIBC (T=2) or to lymph node (N+) or to distant disease (M+), whichever occurs first.;Timepoint(s) of evaluation of this end point: event-free survival (EFS) will be measured as the time from randomization to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints : - Overall CR rate will be measured by determining the proportion of participants with CIS who have no presence of high-risk disease at 6 months. Duration of CR is defined from the time of first CR achieved to first evidence of recurrence, progression or death due to any cause (whichever occurs first) for participants who achieve a CR. - RFS will be measured as the time from randomization to the time of the first recurrence of high-risk disease, or death due to any cause, whichever occurs first. - Time to progression (TTP) will be measured as the time from randomization to the date of first documented evidence of disease progression or death due to disease progression, whichever occurs first. - Overall Survival (OS), defined as the time from randomization to death, due to any cause. For the full list of secondary objectives, please refer the protocol. ;Timepoint(s) of evaluation of this end point: Overall complete response (CR) rate - at 6 months Recurrence-free survival (RFS) -Throughout the Study Time to progression (TTP) -throughout the Study Overall survival (OS) - Defined as the time from the date of randomization to death, from any cause. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Registry group
Janssen-cilag international NV
Outcome results
None listed