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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-Guérin who are Ineligible for or Elected Not to Undergo Radical Cystectomy
EU CTIS ID: 2023-506146-23-00
What this study is testing
To evaluate the overall Complete Response (CR) rate in participants treated with TAR-200 in combination with IV cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or IV cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS) with or without concomitant high-grade Ta or T1 papillary disease. To evaluate DFS in participants treated with TAR-200 alone with papillary disease only (Cohort 4 only).
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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
- Adequate bone marrow, liver, and renal function (creatinine clearance >30 mL/min)
- 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 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. Male participants should consider preservation of sperm prior to study treatment as anticancer treatments may impair fertility. Investigators will advise male participants on the options for banking of sperm for reproductive conservation. A male participant must also agree to not donate sperm for the purpose of reproduction during the study and for at least 6 months after the last dose of study drug, and not plan to father a child while enrolled in this study or within 6 months after the last dose of study drug.
- A female participant of childbearing potential must have a negative serum test at screening and a negative urine test within 72hours 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
- Participants must be willing and able to adhere to the lifestyle restrictions specified in this protocol
- Histologically confirmed diagnosis of persistent or recurrent HRNMIBC, CIS (OR Tis) [AJCC, 2017], 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 of the last dose of BCG therapy, in patients who have received adequate BCG
You likely can't join if
- Presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and/or Stage IV)
- Active infection requiring systemic IV therapy within 14 days prior to randomization
- 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
- Indwelling catheters are not permitted; however, intermittent catheterization is acceptable
- 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
- 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
See the full eligibility criteria
Who can join
- 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
- Adequate bone marrow, liver, and renal function (creatinine clearance >30 mL/min)
- 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 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. Male participants should consider preservation of sperm prior to study treatment as anticancer treatments may impair fertility. Investigators will advise male participants on the options for banking of sperm for reproductive conservation. A male participant must also agree to not donate sperm for the purpose of reproduction during the study and for at least 6 months after the last dose of study drug, and not plan to father a child while enrolled in this study or within 6 months after the last dose of study drug.
- A female participant of childbearing potential must have a negative serum test at screening and a negative urine test within 72hours 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
- Participants must be willing and able to adhere to the lifestyle restrictions specified in this protocol
- Histologically confirmed diagnosis of persistent or recurrent HRNMIBC, CIS (OR Tis) [AJCC, 2017], 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 of the last dose of BCG therapy, in patients who have received adequate BCG
- All visible papillary disease must be fully resected (absent) prior to randomization (residual CIS is 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)
- 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)
- Participants must be ineligible for or have elected not to undergo radical cystectomy
- 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
- All AEs associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE version 5.0 Grade <2 prior to screening
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
What rules you out
- Presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and/or Stage IV)
- Active infection requiring systemic IV therapy within 14 days prior to randomization
- 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
- Indwelling catheters are not permitted; however, intermittent catheterization is acceptable
- 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
- 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
- Not recovered from toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration)
- No clinically significant liver disease that precludes participant treatment regimens prescribed on the study
- 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
- 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 B infection with positive HBsAg antibody and undetectable PCR are allowed)
- Concurrent urinary tract infection, defined as a symptomatic infection with a positive urine culture with a bacterial count of ≥10^5 colony forming units (CFU)/mL in urine voided from women, or >10^4 CFU/mL in urine voided from men, or in straight-catheter urine from women
- No 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 nephroureterectomy more than 24 months prior to randomization
- Known hypersensitivity to gemcitabine (or other drug excipients) or chemically-related drugs
- Known hypersensitivity to the TAR-200 device constituent or the (TAR-200) UPC materials
- Evidence of radiographic features associated with pulmonary fibrosis/advanced interstitial lung disease or active non-infectious pneumonitis
- Participants must not have active tuberculosis
- Major surgery within 4 weeks before screening (TURBT is not considered major surgery)
- Any condition for which participation would not be in the best interest of the participants or that could prevent, limit, or confound the protocol-specified assessments
- 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 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)
- 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
- Evidence of bladder perforation during diagnostic cystoscopy
- Bladder post-void residual volume > 350mL at Screening after second voided urine
- No history of acute ischemic heart disease within 30 days of cohort assignment, or history of uncontrolled cardiovascular disease
- History of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 mL
- 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
The study team makes the final eligibility decision.
Where it's taking place
- United States
- Russian Federation
- Australia
- Ukraine
- Japan
- Canada
- Korea, Republic of
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; Russian Federation; Australia; Ukraine; Japan; Canada and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.