Evaluating Safety and Efficacy of Verity-BCG in BCG-naïve Patients with Intermediate and High-risk Non-muscle Invasive Bladder (NMIBC)

Inclusion Criteria:

• Male or Female

• 18 years and older

• Low or high-grade NMIBC as defined by 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification and Grade 2 or 3 in the 1973 classification, diagnosed within 60 days of registration.

• Pathologically confirmed and completely resected stage Ta or T1 urothelial cellcarcinoma, with or without associated carcinoma in situ (CIS), diagnosed within 60days of registration.

1. Patients with T1 disease must have imaging demonstrating no evidence ofmetastatic disease (based on MRI or CT scan) within 90 days of registration, toconfirm stage T1N0M0 disease.

2. For patients with stage T1 disease, repeat TURBT must be performed as perstandard of care/CUA guidelines.

• Patients may have intermediate or high recurrence risk disease, as indicated by theprobability of 2-year recurrence of ≥ 50% based on the EORTC Bladder Cancer riskcalculator.

• ECOG performance status of 0-2

• Adequate organ and marrow function as defined below:

• leukocytes ≥3,000/mcL

• absolute neutrophil count ≥1,500/mcL

• platelets ≥100,000/mcL

• total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

• creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥50mL/min/1.73 m2 unless data exists supporting safe use of BCG at lower kidneyfunction values, no lower than 30 mL/min/1.73 m2

• For women of childbearing potential involved in any sexual intercourse that couldlead to pregnancy: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during 120 days after the last dose of the studytreatment. Note: The use of contraceptive methods does not apply to subjects who areabstinent for at least 4 weeks before Day 1 and will continue to be abstinent frompenile-vaginal intercourse 120 days after last dose of study drug treatment. Thereliability of sexual abstinence needs to be evaluated in relation to the durationof the clinical trial and the preferred and usual lifestyle of the participant.

• Note: A woman of non-childbearing potential is defined as follows:

• Has had surgical sterilization (hysterectomy, bilateral oophorectomy, orbilateral salpingectomy);

• Has had a cessation of menses for at least 12 months without an alternativemedical cause, and a follicle-stimulating hormone (FSH) test confirmingnonchildbearing potential (refer to laboratory reference ranges forconfirmatory levels).

• Male patients with female partner of childbearing potential must agree to beabstinent or practice an effective method of contraception.

Male patients must agree to refrain from donating sperm during the treatment period and for at least 120 days after the last dose of study treatment.

Exclusion Criteria:

• Presence of urothelial carcinoma involving the upper urinary tract or prostaticurethra documented by radiological imaging or biopsy, performed within 12 months ofthe start of treatment. Should the imaging or biopsy be performed outside the windowit will be up to the physicians' discretion to re-scan/biopsy. This is considered T4disease.

• CIS only disease.

• Pure squamous cell carcinoma or adenocarcinoma.

• Presence of micropapillary components.

• Other prior non-bladder malignancy, except for the following:

• adequately treated basal cell or squamous cell skin cancer.

• in situ cervical cancer.

• adequately treated stage I or II cancer currently in complete remission, or anyother cancer from which the patient has been disease free for five years.

• patients with localized prostate cancer who are being followed by an activesurveillance program are also eligible.

• Prior intravesical BCG or intradermal BCG, with the exception of tuberculosisvaccination in childhood.

• Chronic administration of steroids (>10 mg prednisone) at the time of randomization.

• Current or planned concomitant biologic therapy, radiation therapy, hormonaltherapy, chemotherapy, surgery, or other cancer therapy while on study.

• Prior chemoradiation treatment (trimodal therapy or "TMT") for bladder cancer.

• Currently being treated or scheduled to have treatment with any systemic orintravesical chemotherapeutic agent during the study.

• Receiving any other investigational agents.

• The presence of an impaired immune response irrespective of whether this impairmentis congenital or caused by disease, drugs or other therapy.

• Known positive HIV serology.

• Presence of a urinary tract infection; treatment should be withheld until urineculture is negative and antibiotic therapy is stopped.

• Trauma to the urinary bladder. In case of gross hematuria, therapy should be stoppedor postponed until the hematuria has been successfully treated or has resolved.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to BCG vaccine.

• Uncontrolled intercurrent illness.

• Psychiatric illness/social situations that would limit compliance with studyrequirements.

• Pregnancy: pregnant women are excluded from this study because VERITY-BCG is anagent with the potential for teratogenic or abortifacient effects. Because there isan unknown but potential risk for adverse events in nursing infants secondary totreatment of the mother with VERITY-BCG, breastfeeding should be discontinued if themother is treated with VERITY-BCG.