A Phase III, Open-Label, Multi-Center, Randomized Study Evaluating the Efficacy and Safety of TAR-200 in Combination With Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants With BCG-naïve High-Risk Non-Muscle Invasive Bladder Cancer

Study Identifier:
17000139BLC3002
CT.gov Identifier:
NCT05714202
EudraCT Identifier:
202351000000
EU Trial (CTIS) Number:
2023-507187-39-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

To compare event-free survival (EFS) in participants with BCG-naïve HR--NMIBC (high-grade papillary Ta, any T1, or Carcinoma in Situ [CIS]), receiving TAR-200 in combination with systemic intravenous (IV) cetrelimab versus intravesical BCG.

To assess the efficacy and safety of TAR-200 plus systemic cetrelimab or TAR-200 alone versus BCG in patients with BCG-naive HR NMIBC

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bladder
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    III
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: participants with BCG-naive HR--NMIBC (high-grade papillary Ta, any T1, or Carcinoma in Situ [CIS]), receiving TAR-200 in combination with systemic intravenous (IV) cetrelimab versus intravesical BCG.
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  • Drug: Experimental: Treatment Group A: TAR-200 + Cetrelimab
  • Drug: Group A (n≈350) TAR-200 (225 mg gemcitabine Q3W [induction phase] and Q12W [maintenance phase]) + cetrelimab
  • Drug: Biological: Cetrelimab
  • Drug: Biological: BCG Vesiculture
  • Drug: Experimental: Treatment Group C: TAR-200 Alone
  • Drug: Drug: TAR-200
  • Drug: experimental drug
  • Drug: 2Chinese common name: Cetrelimab
  • Drug: Control drug
  • Drug: Subject are randomized 1: 1:1 to receive TAR-200 + CET (Group A), TAR-200 (Group C) or BCG (Group B). In Groups A and C, TAR-200 (225 mg gemcitabine) is dosed Q3W during an induction phase, then Q12W during a maintenance phase. In Group B, BCG is dosed QW for 6 wks and QW for 3 wks at Wks 12, 24, 48, 72, and 96.
  • Drug: Eligible BCG-naive HR NMIBC patients (N≈1050) will be randomized 1: 1:1 to receive TAR-200 plus cetrelimab, TAR200, or BCG (Figure 2)
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Age
    • 1. Age ≥18 years (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
    • Disease Characteristic
    • 2. Histologically confirmed initial diagnosis by local pathology (within 90 days of the most recent signed informed consent) of high grade non-muscle invasive bladder cancer (HR-NMIBC) (high-grade Ta, any T1 or carcinoma in-situ [CIS]), in participants who are Bacillus Calmette Guérin (BCG)-naïve
    • 3. BCG-naïve (participants who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before date of randomization are eligible) (Kamat 2016).
    • 4. Participants must be willing to undergo all study procedures (eg, multiple cystoscopies from Screening through the end of study and TURBT/bladder biopsy for assessment of
    • recurrence/progression).
    • 5. All visible papillary disease must be fully resected (absent) prior to date of randomization and documented at baseline cystoscopy. Local urine cytology at screening must be negative or atypical (for high-grade urothelial carcinoma [HGUC]) for patients with papillary only disease (without CIS)
    • 6. All AEs associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE version 5.0 Grade <2 prior to date of randomization.
    • Type of Participant
    • 7. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2.
    • 8. Thyroid function tests within normal range or stable per Investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal tests results.
    • 9. Adequate bone marrow, liver, and renal function:
    • A. Bone marrow function (without the support of cytokines or erythropoiesis stimulating agent in preceding two weeks):
    • i. Absolute neutrophil count (ANC) ≥1,000/mm3
    • ii. Platelet count ≥75,000/mm3
    • iii. Hemoglobin ≥8.0 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:
    • i. Creatinine clearance >40 mL/min using the Cockcroft-Gault formula.
    • Sex and Contraceptive/Barrier Requirements
    • For inclusion criteria 10-11 Please see the protocol.
    • Informed Consent
    • 12. 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.
    • 13. Participants must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
    • Eligibility: ≥18 y, ECOG PS 0, 1, or 2, histologically confirmed HR NMIBC (high grade Ta, any T1 or CIS) in BCG-naive pts (no prior BCG or stopped >3 y prior to randomization).
    • Patients with histologically confirmed HR NMIBC (high-grade Ta, any T1, or CIS)
    • • BCG-naive (no prior BCG or last exposure >3 years prior to randomization)
    • Age ≥18 years
    • Eastern Cooperative Oncology Group performance status 0, 1, or 2
    • All visible papillary disease must be fully resected (absent) prior to randomization and documented at baseline cystoscopy. Local urine cytology at
    • screening must be negative or atypical for high-grade urothelial carcinoma in patients with papillary-only disease
    • All adverse events associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE v5.0 grade <2 prior to date
    • of randomization
    Exclusion criteria
    • Disease Characteristics
    • 1. Histologically confirmed, muscle invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (ie, ≥T2).
    • 2. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder (ie, urethra, ureter, or renal pelvis). Ta/any 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.
    • 3. N+ and/or M+ per Blinded Independent central Review (BICR) of computed tomography (CT)/magnetic resonance (MR) Urography and Chest CT.
    • Medical Conditions
    • 4. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. Potential allowed exceptions include the following (others may be allowed with Sponsor approval).
    • a. skin cancer (non-melanoma or melanoma) that is considered completely cured.
    • b. non-invasive cervical cancer treated 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):
    • i. with a Gleason score of 6, treated within the last 24 months or untreated and under surveillance,
    • ii. with a Gleason score of 3+4 that has been treated more than 6 months prior to full study Screening and considered to have a very low risk of recurrence,
    • iii. or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
    • 5. Presence of any bladder or urethral anatomic feature (eg, urethral stricture) that, in the opinion of the Investigator, may prevent the safe insertion, indwelling use, removal of TAR-200, or administration of intravesical BCG. Participants with tumors involving the prostatic urethra in men will be excluded.
    • 6. A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 mL.
    • 7. Received a live virus vaccine within 30 days of planned start of study treatment. Inactivated (non-live) vaccines approved or authorized for emergency use (eg,COVID-19) by local health authorities are allowed.
    • 8. Participants should not have a history of acute ischemic heart disease within 42 days of randomization, or history of uncontrolled cardiovascular disease including any of the following in the 3 months prior to Screening:
    • a. unstable angina,
    • b. myocardial infarction,
    • c. ventricular fibrillation,
    • d. Torsades de Pointes,
    • e. cardiac arrest, or known congestive New York Heart Association Class III-IV heart failure,
    • f. cerebrovascular accident,
    • g. transient ischemic attack, or
    • h. pulmonary embolism or other venous thromboembolism in the 3 months prior to Screening.
    • 9. Indwelling catheters are not permitted; however, intermittent catheterization is acceptable.
    • 10. Participants must not have clinically significant liver disease that precludes participant treatment regimens prescribed on the study (including, but not limited to active viral, alcoholic, or other autoimmune hepatitis, cirrhosis, or inherited liver disease).
    • 11. Active hepatitis B or C infection (for example, participants with history of hepatitis C infection but undetectable hepatitis C virus polymerase chain reaction (PCR) test and participants with history of hepatitis B infection with positive HBsAg antibody and
    • undetectable PCR are allowed).
    • 12. Human immunodeficiency virus (HIV) infection, unless the participant has been on a stable anti-retroviral therapy regimen for the last 6 months or more and has had no opportunistic infections and a CD4 count of >350 in the last 6 months.
    • 13. Participants with congenital immunodeficiencies
    • 14. Evidence of radiographic features associated with pulmonary fibrosis/advanced interstitial lung disease (pulmonary consult may be required by the Investigator) as determined by blinded independent central review (BICR) of chest CT, medical history of pneumonitis/interstitial lung disease, or active non-infectious pneumonitis/interstitial lung disease.
    • 15. Evidence of active tuberculin infection (eg, positive Mantoux test).
    • 16. Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions.
    • 17. Major surgery and/or not fully recovered within 4 weeks before first dose (TURBT is not considered major surgery).
    • 18. Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participants (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Bladder