Bladder cancer
Conditions
Interventions
Cohort 1: TAR-200 and Cetrelimab
Type: Experimental
TAR-200 is placed into the bladder through a urinary placement catheter on Day
0 and will be dosed every 3 weeks (Q3W) for up to the first
24 weeks
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age >=18 years male or female (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent 2. Histologically confirmed diagnosis of persistent or recurrent CIS (or 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 (last dose) of adequate BCG therapy, in patients who have received adequate BCG 3. All visible papillary disease must be fully resected (absent) prior to randomization (residual CIS acceptable for participants eligible for Cohorts 1, 2, and 3 only) and documented in the eCRF at Screening cystoscopy. For patients with papillary disease only (Cohort 4), local urine cytology at screening must be negative or atypical (for HGUC). 4. Participants must be willing to undergo all study procedures (e.g., multiple cystoscopies from Screening through the end of study and TURBT/bladder biopsy for assessment of recurrence/progression) 5. Participants must be ineligible for or have elected not to undergo radical cystectomy 6. 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 7. All AEs adverse events associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE version 5.0 Grade 30 mL/min) 11. Contraceptive use by participants should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. Investigators will advise both male and female participants on the options for banking of sperm and ova, respectively for reproductive conservation a. A female participant must be either of the following: i. Not of childbearing potential ii. Of childbearing potential and practicing true abstinence, or have a sole partner who is vasectomized, or practicing at least 1 highly effective user independent method of contraception Participant must agree to continue the above throughout the study and for 6 months after the last dose of study treatment. Note: If a women becomes of childbearing potential after start of the study, the woman must comply with point ii, as described above. A female participant must also agree to not donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study drug, and not be breastfeeding (including participants temporarily withholding breastfeeding) and not planning to become pregnant during the study and for at least 6 months after the last dose of study drug. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertil
Exclusion criteria
Exclusion criteria: 1. Presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (ie,T2,T3,T4, and/or Stage IV). 2. 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 nephrouretrectomy more than 24 months prior to randomization. 3. Active malignancies (ie progressing or requiring treatment change in the last 24 months prior to randomization) other than the disease being treated under study: a. skin cancer (non-melanoma or melanoma) that is considered completely cured b. non-invasive cervical cancer 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. Localized prostate cancer (N0M0) 4. Presence of any bladder or urethral anatomic feature (eg. urethral stricture) that may prevent the safe insertion, indwelling use, or removal of TAR-200, or passage of a urethral catheter for intravesical chemotherapy, or administration of intravesical BCG. Participants with tumors involving the prostatic urethra in men will be excluded. 5. Evidence of bladder perforation during diagnostic cystoscopy. 6. Bladder post-void residual (PVR) volume >350mL at Screening after second voided urine. 7. No history of acute ischemic heart disease within 30 days of cohort assignment, or history of uncontrolled cardiovascular disease. 8. A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 mL. 9. Received a live virus vaccine within 30 days of planned start 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. 10. Active infection requiring systemic IV therapy within 14 days prior to randomization. 11. Currently participating or has participated in a study of an investigational agent and received study therapy or investigational device within 4 weeks prior to screening. 12. Indwelling catheters are not permitted; however, intermittent catheterization is acceptable. 13. Received serial intervening intravesical chemotherapy or immunotherapy from the time of pre-screening or screening cystoscopy/TURBT to starting study treatment. Peri-operative intravesical chemotherapy prior to study is allowed per institutional guidelines. 14. Prior therapy with an anti-programmed -cell death 1, anti-PD-ligand 2 agent, or with an agent directed to another co-inhibitory T-cell receptor. 15. Not recovered from toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration). 16. No clinically significant liver disease that precludes participant treatment regimens prescribed on the study. 17. Human immunodeficiency virus (HIV) infection, unless the participant has been on a stable anti-retroviral therapy regimen for the last 6 months or more prior to randomization and has had no opportunistic infections and a CD4 count of >350 in the last 6 month
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohorts 1, 2, and 3: Overall Complete Response (CR) Rate Up to 5 years Overall CR rate, is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point. Cohort 4: Disease-free surivival (DFS) rate DFS rate is defined as the time from treatment to recurrence, progression or death due to any reason. Twelve-month DFS rate will be determined. | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response (DOR) - Up to 5 years DOR is defined from the date of first CR achieved to the date of first evidence of recurrence or progression or death (whichever is earlier) for participants who achieve a CR. Overall Survival (OS) - Up to 5 years OS, defined as the time from the date of first dose of study treatment to death; if a participant has not died at the time of analysis, the participant will be censored at the date last known alive. Cohort 1, 2 and 4: Concentrations of Gemcitabine and 2*,2* difluorodeoxyuridine (dFdU) in Urine and Plasma - Up to Week 21 Concentrations of gemcitabine and its metabolite dFdU in urine and plasma will be assessed. Cohort 1 and 3: Serum Concentration of Anti-cetrelimab Antibodies - Predose, up to 3 years Serum concentration of anti-cetrelimab antibodies will be assessed using a validated immunoassay for anti-drug antibody (ADA) analysis. Number of Participants with Anti-cetrelimab Antibodies - Predose, up to 3 years Number of participants with anti-cetrelimab antibodies will be reported. Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores - Baseline, up to 3 years and 4 months EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It incorporates 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 symptom scales (fatigue, pain, and nausea or vomiting), and a global health status or HRQoL scale. Ratings for each item range from 1 (not at all) to 4 (very much). Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores - Baseline, up to 3 years and 4 months EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement t | — |
Countries
Netherlands
Outcome results
None listed