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: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10046720Term: Urothelial carcinoma bladder stage IISystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10046721Term: Urothelial carcinoma bladder stage IIISystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10046722Term: Urothelial carcinoma bladder stage IVSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-11
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

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

Inclusion Criteria

1. =18 years (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent
2. Histologically proven, cT2-T4a N0, M0 infiltrating urothelial carcinoma of the bladder. Initial diagnosis must have been within 90 days of randomization date. Participants with variant histologic subtypes (e.g. squamous cell carcinoma) are allowed if urothelial (transitional cell) differentiation is predominant (e.g. <20% variant histologic subtype). However, the presence of any neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features 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 have resolved 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 within normal range or stable on hormone supplementation per investigator assessment. 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.
8. Contraceptive use by men or women 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, 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 female participant becomes of childbearing potential after start of the study, the female participant must comply with point (ii), as described above.
A female 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 drug, 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. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility. Investigators will advise female participants on the options for banking of ova for reproductive conservation.
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 t

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.
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 2 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, known or suspected autoimmune disease.
15. 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.
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 that precludes participant treatment regimens prescribed on the study
22. Human immunodeficiency virus (HIV) infection,

Study & Design

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