Phase 2b Clinical Study Evaluating Efficacy and Safety of TAR-200 in Combination with Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants with High-Risk Non-Muscle Invasive Bladder Cancer Unresponsive to Intravesical Bacillus Calmette-Guerin who are Ineligible for or Elected Not to Undergo Radical Cystectomy

Phase 1

• Conditions: on-Muscle-Invasive Urothelial Carcinoma (NMIBC) of the Bladder; MedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10046721Term: Urothelial carcinoma bladder stage IIISystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10046720Term: Urothelial carcinoma bladder stage IISystem 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: EUCTR2020-002646-16-IT
• Lead Sponsor: JANSSEN CILAG INTERNATIONAL NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-24
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 200

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 high-risk, non-muscle invasive urothelial carcinoma in situ (CIS; Tis) [AJCC, 2017], with or without papillary disease (T1, high-grade Ta) within 12 months of completion of adequate BCG therapy.
3. Visible papillary disease must be fully resected (absent) prior to randomization (residual CIS acceptable) and documented at screening cystoscopy.
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 doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or 2 of 6 doses of a second induction course.
7. All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE version 5.0 Grade <2 prior to screening.
8. Participants must sign the informed consent form (ICF) 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.
9. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2.
10. Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment.
11. Adequate bone marrow, liver, and renal function
12. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies.
13. A woman of childbearing potential must have a negative pregnancy test (ß-hCG) (serum)
within the Screening period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1. Histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and/or Stage IV).
2. Concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
3. Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study.
4. 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.
5. Evidence of bladder perforation during diagnostic cystoscopy.
6. Bladder post-void residual (PVR) volume > 350mL at Screening after second voided urine.
7. Participants should not have a 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. Participants with an active, known or suspected autoimmune disease. Participants with autoimmune disorders not requiring systemic treatment (e.g. skin conditions such as vitiligo, psoriasis, alopecia) or conditions requiring hormonal replacement therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll.
10. Received a live virus vaccine within 30 days of planned start of study treatment.
11. Active infection requiring systemic therapy.
12. Has had an allogeneic tissue/solid organ transplant.
13. 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.
Please see the protocol for the remaining exclusion criteria

Study & Design

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