ADSTILADRIN (=INSTILADRIN) in Patients With High-Grade, Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

Inclusion Criteria

• •1. Aged 18 years or older at the time of consent
• •2. Able to give informed consent
• •3. Had, at entry, confirmed by a pathology report:
• •Carcinoma in situ (CIS) only; Ta/T1 high-grade disease with concomitant CIS; or Ta/T1 high-grade disease without concomitant CIS
• •4. Are "BCG Unresponsive" which refers to patients with high-grade NMIBC who were unlikely to benefit from and who did not receive further intravesical BCG. The term "BCG unresponsive" included patients who did not respond to BCG treatment and had a persistent high-grade recurrence within 12 months after BCG was initiated, and those who despite an initial complete response (CR) to BCG, relapsed with high-grade CIS within 12 months of their last intravesical treatment with BCG or relapsed with high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG. The following criteria defined the patients who were eligible for inclusion in the study:
• •* Had received at least 2 previous courses of BCG within a 12 month period. This was defined as at least 5 of 6 induction BCG instillations and at least 2 out of 3 instillations of maintenance BCG, or at least 2 of 6 instillations of a second induction course, where maintenance BCG was not given;
• •* Exception: those who had T1 high-grade disease at first evaluation after induction BCG alone (at least 5 of 6 doses) qualified in the absence of disease progression.
• •* At the time of tumor recurrence, patients with CIS alone or high-grade Ta/T1 with CIS were within 12 months of last exposure to BCG and patients with high-grade Ta/T1 without CIS were within 6 months of last exposure to BCG;
• •* No maximum limit to the amount of BCG administered; and
• •* All visible papillary tumors were required to be resected and those with persistent T1 disease on transurethral resection of bladder tumor (TURBT) underwent an additional re-TURBT within 14 to 60 days prior to beginning study treatment. Obvious areas of CIS should also be fulgurated.
• •5. Available for the whole duration of the study
• •6. Life expectancy \>2 years, in the opinion of the investigator
• •7. Eastern Cooperative Oncology Group (ECOG) status 2 or less
• •8. Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or magnetic resonance imaging (MRI) with or without urogram performed within 6 months of enrollment
• •9. Patients with prostate cancer on active surveillance at low risk for progression, defined as Prostate-Specific Antigen (PSA) \< 10 ng/dL, Gleason score 6 and clinical stage tumor-1 (cT1) were permitted to be in the study at the discretion of the investigator (see exclusion criterion 10).
• •10. Female patients of childbearing potential were required to use maximally effective birth control during the period of therapy, were required to use contraception for 1 month following the last study drug infusion and were required to have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female patients were required to be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile. 'Maximally effective birth control' meant that the patient, if sexually active, used a combination of two methods of birth control that were approved and recognized to be effective by Regulatory Agencies
• •11. Male patients were required to be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion; and
• •12. Adequate lab values