A Phase 3, Multi-center, Randomized Study Evaluating Efficacy of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder who are not Receiving Radical Cystectomy

Phase 1

• Conditions: Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder; MedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10046720Term: Urothelial carcinoma bladder stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10046721Term: Urothelial carcinoma bladder stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10046722Term: Urothelial carcinoma bladder stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-002620-36-DE
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-02
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

1. =18 years at the time of informed consent.
2.Histologically proven, cT2-T4a N0, M0 urothelial carcinoma of the bladder. Initial diagnosis must have been within 120 days of randomization date. Participants with variant histologic subtypes (e.g. squamous cell carcinoma) are allowed if urothelial (transitional cell) differentiation is predominant. However, the presence of small cell or neuroendocrine variants will make a participant ineligible.
3. Ineligible for or have elected not to undergo radical cystectomy.
4. All adverse events associated with any prior surgery and/or intravesical therapy must haveresolved to CTCAE version 5.0 Grade < 2 prior to randomization.
5. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2.
6.Thyroid function tests are within the normal range per investigator assessment (or stable on hormone supplementation). Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal test results.
7. Adequate bone marrow, liver, and renal function:
a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding 2 weeks): i. Absolute neutrophil count (ANC) = 1,500/mm^3 ii. Platelet count =80,000/mm^3 iii. Hemoglobin =9.0 g/dL
b. Liver function: i. Total bilirubin =1.5 x ULN OR direct bilirubin =ULN for participants with total bilirubin levels >1.5xULN (except participants
with Gilbert's Syndrome, who must have a total bilirubin <3.0 mg/dL), ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =
2.5x institutional ULN
c. Renal function: Creatinine clearance =30 mL/min using the Cockcroft-Gault formula. 24-hour creatinine clearance test will also be accepted for estimating renal function in situations where Cockcroft-Gault formula is not a good predictor of estimating adequate renal function. Note: If cisplatin is chosen as the radio-sensitizing agent, creatinine clearance must be =50 mL/min.
8. 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. A 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), as described above. A participant must also agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 6 months after the last dose of study treatment, and 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. Participants should consider preservation
of eggs prior to study treatment as anti-cancer treatments may impair fertility. Investigators will advise participants on the options for banking
of ova for reproductive conservation.
b. Participants must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any

Exclusion Criteria

1. Active malignancies other than the disease being treated under study.
2. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder.
3. Must not have diffuse carcinoma in situ based on cystoscopy and biopsy. Diffuse, or multi-focal, CIS is defined as the presence of at least
4 distinct CIS lesions in the bladder at the time of the Screening re-TURBT.
4. Participants must not have evidence of cT4b, or N1-3, or M1 disease based on local radiology staging within 42 days prior to randomization.
5. 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.
6. Evidence of bladder perforation during diagnostic cystoscopy. Participant is eligible if perforation has healed prior to randomization.
7. Bladder post-void residual volume >350 mL at screening after second voided urine.
8. History of clinically significant polyuria with recorded 24-hour urine volumes greater than 4,000-mL.
9. Currently participating or has participated in a study of an investigational agent and received study therapy or investigational
device within 4 weeks prior to randomization.
10. Received intervening serial intravesical chemotherapy or immunotherapy from the time of pre-screening (diagnostic) or screening
(completion) cystoscopy/Transurethral Resection of Bladder Tumor to starting study treatment. Peri-operative intravesical chemotherapy prior
to study treatment is allowed per institutional guidelines.
11. Prior therapy with an anti-programmed cell death 1, anti-PD-ligand agent, or with an agent directed to another co-inhibitory T-cell receptor.
12. Participants with a history of Grade =3 toxic effects when using anti-TNF or anti-IL-6 agents.
13. Received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to starting study
treatment or not recovered from adverse events due to a previously administered agent. Participants with a history of prior pelvic radiotherapy are excluded
14. An active autoimmune disease that has required systemic treatment in the past 2 years are excluded.
15. Received a live virus vaccine within 30 days prior to he 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.
16. Active infection requiring systemic IV therapy within 14 days prior to randomization.
18. A pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted if it does not
interfere with placement or retention of TAR-200 in the bladder. Participants with unilateral hydronephrosis are permitted; however,
participants with bilateral hydronephrosis are excluded.
19. Indwelling urinary catheters are not permitted; however, intermittent catheterization is acceptable.
20. Participants who require immunosuppressive medications including but not limited to systemic corticosteroid at doses >10 mg/day of
prednisone or its equivalence, methotrexate, cyclosporine, azathioprine, and TNF-alpha blockers. Use of immunosuppressive medications for the
management of immune related adverse events, infusion related reactions, or in participants with contrast allergies is acceptable. Use of
inhaled, topical, and intranasal corticosteroids are permitted.
21. Must not have clinically significant liver disease t

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified