Clinical Trials

Inclusion Criteria:

To participate in this study, all subjects must meet all inclusion criteria described:

• Male or female subjects, 18 years of age or older at the time of signing the informed consent.
• Subjects who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry.
• Subjects with a histologically confirmed, high-grade Ta or CIS urothelial cell carcinoma of the bladder according to American Joint Committee on Cancer staging and 2016 WHO/ISUP grading classification (Amin et al. 2017, Moch et al. 2016).
  • Note:  Slides from the subject’s diagnosis of HGTa or CIS within 36 months of signing the informed consent will be sent for central review to assess.
• Bladder cancer stage CIS with concomitant Ta are eligible. However, all visible papillary tumors must be removed prior to treatment.
• Subjects with histologically confirmed HGTa or CIS NMIBC (including CIS with concomitant Ta) will be enrolled in the dose escalation phase (Phase 1a) Subjects with CIS NMIBC (including CIS with concomitant Ta) with active disease (defined as disease present at last cystoscopic evaluation) will be enrolled in the dose expansion phase (Phase 1b).
• Subjects who are unable to obtain intravesical BCG for the treatment of NMIBC, have received at least one dose of intravesical BCG, or at least one dose of intravesical chemotherapy.
• Subjects enrolled in other clinical treatment studies (other than studies with intravesical or systemic immunotherapies for NMIBC) should have received their last treatment at least 6 weeks prior to the time of signing the informed consent (i.e., 6-week washout period for therapies other than in NMIBC; those who were previously enrolled in treatment studies for NMIBC are excluded).
• Subjects who the Investigator believes can and will comply with the requirements of the protocol.
• Subjects with an ECOG performance status of 0, 1 or 2.
• If sexually active with male partners, the female of childbearing potential agrees to use a medically acceptable method of contraception for the duration of the study and for at least 4 weeks after the last dose of investigational product. Females are considered of childbearing potential if they are post-menarche, have not been surgically sterile for at least 6 weeks (i.e., total hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation) and are pre-menopausal (menopause is defined as complete cessation of menstruation for at least 12 months). Acceptable methods of contraception include:
  • The simultaneous use of stable hormonal contraception in conjunction with a double-barrier method (e.g., condom with spermicide or diaphragm with spermicide), or;
  • The use of an intrauterine device in place for at least 12 weeks, in conjunction with a double barrier method, or;
  • Abstinence if this is the subject’s usual lifestyle and preferred contraception;
• If sexually active with female partners, the sexually mature, nonsterile male agrees to use a medically acceptable method of contraception for the duration of the study and for at least 4 weeks after the last dose of investigational product. Males are considered surgically sterile if they have undergone bilateral orchiectomy or vasectomy at least 12 weeks prior to signing informed consent. Acceptable methods of contraception include:
  • The simultaneous use of stable hormonal contraception by the female partner in conjunction with a double-barrier method (e.g., condom with spermicide or diaphragm with spermicide), or;
  • The female partner’s use of an intrauterine device in place for at least 12 weeks, in conjunction with a double barrier method, or;
  • The female partner is surgically sterile for at least 6 weeks or is at least 12 months postmenopausal, or;
  • Abstinence if this is the subject’s usual lifestyle and preferred contraception.
• Females of childbearing age with a negative pregnancy test.
• Subjects whose treating physician must confirm availability and access to TARA-00.
• Subjects who have not completed vaccination against COVID-19 with a negative PCR.
• SARS-CoV-2 diagnostic test.

Exclusion Criteria:

To participate in this study, subjects must not meet ANY exclusion criteria described below:

• Penicillin allergy (subjects with a questionable history of allergy to penicillin or no history of penicillin use will undergo sensitivity testing prior to inclusion in the study).
• Predominant (defined as > 50%) adenocarcinoma, squamous cell carcinoma, or histological variants including plasmacytoid, sarcomatoid, or squamous components (Note: if predominant histology is urothelial, the subject is eligible for the study).
• Subjects with any micropapillary component or lymphovascular invasion will be excluded.
• Prostatic involvement, upper tract urothelial carcinoma, nodal involvement, or metastatic disease.
• Bladder cancer stage ≥ T1 according to American Joint Committee on Cancer staging criteria (Amin et al. 2017).
• Bladder cancer stage CIS with concomitant T1.
• Hydronephrosis on radiographic imaging.
• Life expectancy of less than 5 years.
• ECOG performance status 3 or 4.
• Has received prior radiotherapy to the pelvis.
• Has significant urinary incontinence or otherwise unable to hold intravesical.
• immunotherapy in the bladder for 2 hours, per the Investigator’s judgment.
• Concurrent or planned treatment with intravesical or systemic immunotherapy during the study period.
• Concurrent or planned biologic therapy, hormonal therapy (other than oral contraception), chemotherapy, surgery (other than TURBT or biopsy), or other cancer therapy during study period.
• Concurrent malignancy diagnosed within 6 months prior to the time of signing the informed consent. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, or low or very low risk prostate cancer under active surveillance.
• Participation in any other interventional clinical study within 6 weeks prior to signing informed consent.
• Inadequate organ and bone marrow function defined as:
  • Hemoglobin ≤ 8.0g/dL;
  • Absolute neutrophil count ≤ 1.5 x 10^9 / L;
  • Platelet count ≤ 80 x 10^9 / L;
  • AST/SGOT and/or ALT/SGPT ≥ 2.5 x ULN;
  • Total bilirubin >1.0 x ULN;
  • Estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73m^2 per the Cockroft-Gault equation:
  • [(140 - age) x wt (kg) x 0.85 (if female)] / [72 x creatinine (mg/dL)].
• Current indwelling ureteral stent.
• A woman who is nursing, pregnant, or intending to become pregnant during the study period.
• Known human immunodeficiency (HIV) infection or other immunodeficiency disorders, either primary or acquired. Exceptions include subjects requiring use of inhaled or intranasal corticosteroids or local steroid injections.
• In the opinion of the treating Investigator, the subject has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate.

Eligibility last updated 10/6/21. Questions regarding updates should be directed to the study team contact.