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
- Conditions
- on-Muscle-Invasive Urothelial Carcinoma (NMIBC) of the BladderMedDRA 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
- EUCTR2020-002646-16-NL
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 200
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 <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. Adequate bone marrow, liver, and renal function (creatinine
clearance >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 fertility. Investigators will advise female participants on the options of banking of ova for reproductive conservation.
b. A male participant must wear a condom (with or without
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 months.
18. Active hepatitis B or C infection (for example, participants with history of hepatitis C infection but undetectable hepatitis C virus PCR test and participants with history of hepatitis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method