A Phase 2, Open-Label, Multi-Center, Randomized Study of TAR-200 in Combination with Cetrelimab and Cetrelimab Alone in Participants with Muscle-Invasive Urothelial Carcinoma of the Bladder who are Scheduled for Radical Cystectomy and are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy
- Conditions
- Muscle-Invasive Urothelial Carcinoma of the BladderMedDRA version: 20.0Level: LLTClassification code: 10046714Term: Urothelial carcinoma bladder Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-507189-17-00
- Lead Sponsor
- Janssen - Cilag International
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
1. =18 years (or the legal age of consent where the study takes place), 10. All adverse events associated with any prior surgery must have resolved to CTCAE version 5.0 Grade <2 prior to randomization, 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 participants on the options for banking of sperm and ova for reproductive conservation. A female participants must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment 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 participant becomes of childbearing potential after start of the study, the participant must comply with point (ii) A female participant must also: • agrees 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 treatment • not be breastfeeding and not planning to become pregnant during the study and for at least 6 months after the last dose of study treatment b. A male participant must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 6 months after receiving the last dose of study treatment. His female partner, if of childbearing potential, must also be practicing a highly effective method of contraception. If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception. A male participant must also: • agree to not donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after the last dose of study treatment • not plan to father a child while enrolled in this study or within 6 months after the last dose of study treatment, 12. A female participant of childbearing potential must have a highly sensitive negative serum (ß-human chorionic gonadotropin [ß-hCG]) or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study, that may exceed those listed in the Schedule of Activities, 13. Must sign an ICF (or their legally acceptable representative must sign), 2. Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma (AJCC 2017) 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, 3. Participants with no residual tumor, or intravesical tumor size of =3 cm following TURBT are eligible; debulking TURBT for any residual disease is encouraged but not mandated. Participants with persistent tumors >3 cm at screening must undergo a second debulking, re-staging TURBT Participants will be ineligible
1. Active malignancies other than the disease being treated under study, 10. Criterion - deleted per Amendment 1, 11.Pyeloureteral tube externalized to the skin is exclusionary, 12. Indwelling catheters are not permitted, 13. Participants with an active autoimmune disease that required systemic treatment in the past 2 years, 14. Participants must not have clinically significant liver disease that precludes participant treatment regimens prescribed on the study, 15.Human immunodeficiency virus infection, 16.Evidence of active or chronic hepatitis B or C infection, 17.Concurrent urinary tract infection (UTI), that cannot be cleared with antibiotic therapy, 18.Criterion deleted per Amendment 2, 19.Evidence of interstitial lung disease or active non-infectious pneumonitis., 2. Must not have received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study treatment, 20.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements, 21.Participants with current acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation, and participants who have a history immune-mediated colitis, 22.Criterion deleted per Amendment 2, 23.Not recovered from adverse events due to a previously administered agent, 24.Prior systemic chemotherapy for urothelial cell carcinoma of the bladder at any time., 25.Pelvic radiotherapy administered less than 6 months prior to screening, 26.Received a live virus vaccine within 30 days of initiation of study treatment. Inactivated (non-live or non-replicated) vaccines approved or authorized for emergency use (eg, Coronavirus Disease 2019 [COVID19]) are allowed, 27.Criterion deleted per Amendment 2, 28.Active infection requiring systemic intravenous therapy within 14 days prior to randomization., 29.Received intervening intravesical chemotherapy or immunotherapy from the time of most recent cystoscopy/TURBT to starting study treatment. Immediate post-TURBT single-dose peri-operative intravesical chemotherapy is allowed per institutional guidelines in the screening phase., 3. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder, 30.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, antiCD137, or anti cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways., 31.Participants with a history of Grade =3 toxic effects when using antiTNF or anti-IL-6 agents are excluded., 32.Participants still recovering from toxicity of prior anticancer therapy which was received more than 24 months prior to enrollment (except toxicities which are not clinically significant such as alopecia, skin discoloration)., 33.Participants who require immunosuppressive medications, 34.Participants with a history of allergy to protein-based therapies and participants with a history of any significant drug allergy are excluded., 35.Known hypersensitivity to any study component including: a.Gemcitabine (or other drug excipients) or chemically-related drugs, b.TAR-200 device constituent materials, c.TAR-200 Urinary Placement Catheter materials, d.Cetrelimab excipients or chemically-related drugs Refer to t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the anti-tumor effects of TAR 200 + Cetrelimab (Cohort 1) and Cetrelimab alone (Cohort 2);Secondary Objective: To evaluate the safety and tolerability of up to 4 dosing cycles of TAR200 + cetrelimab (Cohort 1) and cetrelimab (Cohort 2) alone prior to RC • To determine the recurrence-free survival (RFS) in participants receiving TAR-200 + cetrelimab (Cohort 1) and cetrelimab alone (Cohort 2);Primary end point(s): pCR rate at radical cystectomy (RC)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):• Frequency and grade of AEs • Laboratory abnormalities • Recurrence-free survival (RFS)