PIVOT-006
A Phase 3, Randomized Study of Adjuvant Cretostimogene Grenadenorepvec versus Observation for the Treatment of Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) Following Transurethral Resection of Bladder Tumor (TURBT)
Inclusion Criteria:
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Pathologically confirmed within 90 days of study randomization:
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Recurrent low-grade Ta (LG Ta) within 12 months of prior low-grade or high-grade (high-grade Ta [HG Ta] ≤3 cm) tumor
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Solitary LG Ta >3 cm
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Multifocal LG Ta
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Primary and solitary HG Ta ≤3 cm
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Low-grade T1 (LG T1)
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Has had all visible disease removed by TURBT at Baseline within 12 weeks of study randomization, prior to study treatment or initiation of observation period.
Exclusion Criteria:
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Has current or prior evidence of high-risk NMIBC defined as: HG T1, HG Ta >3 cm (recurrent or multifocal), CIS, variant histology, lymphovascular invasion, and T2
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Low Risk NMIBC: LG Ta ≤3 cm, that has recurred more than 12 months after a previous high-grade (HG Ta ≤3 cm) or low-grade tumor.
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Has Hx of LG or HG UT UCC within 24 months prior to randomization
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Has had prior treatment with any human adenovirus serotype 5 based therapy
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Immunocompromised
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Active Infection requiring systemic therapy
Principal Investigator:
enGene
A Phase 1/2 Study of EG-70 as an Intravesical Administration to Patients with BCG-Unresponsive NMIBC and High-Risk NMIBC Patients who are BCG Naïve or Received Incomplete BCG Treatment (Phase 2)
Inclusion Criteria:
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BCG-unresponsive NMIBC with (CIS) w/ or w/o resected papillary tumors indicated for, ineligible for, or have elected not to undergo cystectomy:
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persistent HG Ta, T1, or Tis after receiving iBCG (at least 5/6) or recurrence after 12 mo. of receiving iBCG (at least 5/6) or
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T1 high grade disease residual at the first evaluation following iBCG (at least 5/6)
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Patients previously treated with investigational or approved checkpoint inhibitor (e.g., pembro) who failed treatment are eligible for inclusion 30 days post-treatment
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Male or non-pregnant, non-lactating female
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ECOG 0, 1 or 2
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Hematologic inclusion w/i 2 wks of tx:
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a. Absolute neutrophil count >1,500/mm3.
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b. Hemoglobin >9.0 g/dl.
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c. Platelet count >100,000/mm3.
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Hepatic inclusion w/i 2 wks of Day 1:
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Total bilirubin ≤1.5 ULN
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Creatinine clearance >30 mL/min (measured using Cockcroft-Gault or eGFR)
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AST and ALT ≤2.5 x ULN for the institution, alkaline phosphatase ≤2.5 x ULN for the institution, unless bone metastasis is present in the absence of liver metastasis.
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PT and PTT w/i normal limits at Screening.
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Must be able to retain study drug for 60 min
Exclusion Criteria:
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Any other malignancy diagnosed w/i 1 yr of study entry (except basal or squamous cell skin cancers or noninvasive cancer of the cervix)
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Concurrent tx with any chemotherapeutic agent.
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Treatment with pembro w/i 30 days prior to Screening.
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Treatment with last therapeutic agent w/i 30 days of Screening
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Hx vesicoureteral reflux or indwelling urinary stent.
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Participation in any other research protocol involving administration of an investigational agent within 1 mo prior to Day 1.
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Hx external beam radiation to the pelvis at any time or prostate brachytherapy w/i last 12 mo
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Hx interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
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Evidence of metastatic disease.
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Hx difficult catheterization that would prevent administration of EG-70.
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Hx interstitial cystitis.
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Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
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Known HIV, Hep B, or Hep C
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Significant cardiovascular risk (e.g., coronary stenting within 8 wks, myocardial infarction within 6 mo).
Principal Investigator:
ABLE-22
A Phase 2, Randomized, Multi-Center, Open Label Trial to Evaluate the Safety and Efficacy of Intravesical Nadofaragene Firadenovec Alone or in Combination with Chemotherapy (Gemcitabine and Docetaxel) or Immunotherapy (Pembrolizumab) in Subjects with High-Grade Bacillus Calmette-Guerin (BCG) Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC).
Inclusion Criteria:
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Diagnosed with CIS ± Ta/T1 high-grade disease.
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Unresponsive to ≥ 2 courses of BCG therapy within the last 12 months.
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All visible papillary tumors must be resected and those with persistent T1 disease on TURBT should undergo an additional re-TURBT.
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Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Subjects with prostate cancer on active surveillance at low risk are permitted.
Exclusion Criteria:
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Current or prior evidence of muscle-invasive or metastatic disease.
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Current systemic therapy for bladder cancer other than IMP used in randomization arm.
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Current or prior investigational treatment for BCG-unresponsive NMIBC or any other investigational drug within 1 month prior to screening.
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Current or prior pelvic external beam radiotherapy within 5 years of screening.
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Prior treatment with nadofaragene firadenovec at any time.
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Prior systemic therapy for bladder cancer at any time.
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Immunocompromised.
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Unexplained elevated liver or renal function tests.
Principal Investigator:
ABLE-32
A Phase 3b, Randomised, Controlled Trial of Nadofaragene Firadenovec vs. Observation in Subjects with Intermediate Risk (IR) Non-Muscle Invasive Bladder Cancer (NMIBC).
Inclusion Criteria:
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Newly diagnosed or recurrent intermediate risk (IR) NMIBC at screening
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Has undergone complete transurethral resection of bladder tumor (TURBT; with or without peri-operative intravesical chemotherapy) within 60 days prior to randomization, with 1 of the following confirmed by a diagnostic pathology report:
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Recurrence within 1 year, low-grade Ta
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Solitary low-grade Ta >3 cm
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Low-grade Ta, multifocal
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Solitary high-grade Ta, ≤3 cm
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Low-grade T1a
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Exclusion Criteria:
- Has current or prior evidence of high-risk NMIBC defined as: HG T1, HG Ta >3 cm (recurrent or multifocal), CIS, variant histology, lymphovascular invasion, and T2
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Current or previous evidence of muscle-invasive or metastatic disease presented at the screening visit
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Low-risk NMIBC defined as: First occurrence of low-grade solitary Ta ≤3 cm; Recurrence of low-grade solitary Ta ≤3 cm >12 months from previous occurrence; and or papillary urothelial neoplasm of low malignant potential
Principal Investigator:
ABLE-41
ADSTILADRIN Early Utilization and in the Real World Setting in US.
Inclusion Criteria:
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Prescribed and scheduled treatment with ADSTILADRIN
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Received the first instillation of ADSTILADRIN after 5 September 2023
Exclusion Criteria:
- Currently enrolled in a clinical trial
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Patients who have previously been treated with ADSTILADRIN in the context of a clinical trial
Principal Investigator:
BOND-003
A Phase 3 Study of Cretostimogene Grenadenorepvec in Patients with Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG).
Inclusion Criteria:
- ECOG performance status of 0 to 2.
- Have pathologically confirmed BCG-unresponsive HG Ta/T1 papillary disease without CIS.
- Pathologically confirmed recurrent HG Ta/T1 papillary disease without CIS within
- 6 months of completion (last dose) of adequate BCG treatment for HGUC (e.g., CIS,
- HG Ta, HG T1, or a combination of these HGUC pathologies).
- Patients with HG Ta: Completion of qualifying BCG treatment within 12 months of the initial qualifying dose of BCG
- All pathology specimens must be predominantly urothelial (transitional cell) and have less than 50% variant histology.
- Have all Ta and/or T1 disease resected, prior to study treatment
- Ineligible to receive radical cystectomy (medically unfit) or refusal of radical cystectomy
- Demonstrate adequate organ function
- Willing to use barrier contraception.
Exclusion Criteria:
- Has current or past history of muscle invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer.
- Any HGUC as T1, HG Ta, or CIS in the upper genitourinary tract or prostatic urethra within 24 months OR any history of T2 or higher stage urothelial carcinoma in the upper genitourinary tract
- Has received systemic anti-cancer therapy, including investigational agents
- Has had prior systemic treatment
- Has had prior treatment with any human adenovirus serotype 5 based therapy
- Has used excluded anti-viral medication
- Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended
- Has significant immunodeficiency due to underlying illness
- Has had prior organ or allogenic stem cell transplant.
- Has known active Hepatitis B or Hepatitis C virus
- Has current or prior pelvic (including the bladder) external beam radiotherapy
- Has a history of another malignancy within 3 years except localized, low-risk, prostate cancer
- Cancers with negligible risk of metastasis or death
- Has an active infection requiring systemic therapy
- Has had active autoimmune or inflammatory disease requiring systemic treatment
- Pregnant, currently breastfeeding or intending to breastfeed
- Has received a live vaccine within 30 days prior to the first dose of study drug.
Principal Investigator:
BLCC Registry
Blue Light Cystoscopy with Cysview (BLC with Cysview) Registry
Inclusion Criteria:
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Suspected or known non-muscle invasive bladder cancer on the basis of a prior cystoscopy, or undergoing surveillance cystoscopy for carcinoma of the bladder
Exclusion Criteria:
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Porphyria
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Gross hematuria
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Known hypersensitivity to hexaminolevulinate or aminolevulinate derivatives