This study will evaluate the safety and efficacy of intravesical administration of detalimogene (EG-70) in the bladder and its effect on bladder tumors in patients with NMIBC.
This study study consists of two phases; a Phase 1 dose-escalation to establish safety and recommended the phase 2 dose, followed by a Phase 2 study to establish how effective the treatment is. The Study will include patients with: NMIBC with CIS for whom BCG therapy is unresponsive, and other high risk patients with NMIBC.
A Substudy will include a surfactant bladder rinse prior to the instillation of detalimogene in patients with NMIBC with CIS for whom BCG therapy is unresponsive.
BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without coexisting papillary Ta/T1 tumors who are ineligible for or have elected not to undergo cystectomy, and have experienced CIS disease within 12 months of treatment where: adequate BCG regimen consists of at least 2 courses of BCG where the first course (induction) must have included at least 5 or 6 doses and the second course may have included a re-induction (at least 2 treatments) or maintenance (at least 2 doses), and Cis must be documented or indicated by pathology
Patients who have previously been treated with a checkpoint inhibitor and failed treatment are eligible for inclusion 30 days post-treatment (Phase 1) or 3 months post-treatment (Phase 2).
Male or non-pregnant, non-lactating female, 18 years or older.
Women of childbearing potential must have a negative pregnancy test at Screening.
Active malignancies (i.e., progressing or requiring treatment change in the last 24 months). Exceptions allowed under Sponsor review.
Concurrent treatment with any chemotherapeutic agent.
History of partial cystectomy.
Treatment with last therapeutic agent (including intravesical chemotherapy post-TURBT) within 30 days of Screening (prior to the screening biopsy).
Sequential
EG-70 (phase 1)
DrugPatients will receive up to four cycles of EG-70 administered as a bladder instillation of a 50 mL volume of study drug via catheter with a targeted retention time of 60 minutes.One cycle lasts approximately 12 weeks and consists of either a 2-dose (Day 1 and Day 8) or 4-dose (Day 1, Day 8, Day 29 and Day 36) regimen.
EG-70 (phase 2) Master Protocol
DrugUnder the Treatment Period, patients will receive 4 instillations per cycle for up to 4 cycles, of EG-70 at the RP2D defined in Phase 1, administered as a bladder instillation of a 50 mL volume of study drug via catheter with a targeted retention time of 60 minutes. One cycle lasts approximately 12 weeks. For Maintenance treatment 2 doses of EG-70 will be administered as a bladder instillation per 12-week cycle.
Surfactant Bladder Pre-Rinse and EG-70 (Substudy)
DrugPatients will receive via catheter a 50 mL volume of a 5-minute bladder rinse immediately prior to administration of 50 mL of detalimogene voraplasmid (EG-70) at the RP2D for 30 minutes. During the Treatment Period, patients will receive 4 instillations per cycle for up to 4 cycles of the sudy intervention. One cycle lasts approximately 12 weeks. For Maintenance treatment, 2 doses of the study intervention will be administered as a bladder instillation per 12-week cycle.
Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0.
The type, incidence, relatedness and severity of treatment emergent adverse events of EG-70 as assessed by NCI-CTCAE V5.0 will be monitored.
Phase 2: Percentage of patients with cystoscopic CR at any time, based on exam, urine cytology and appropriate biopsies.
Complete response rate will be measured by determining the number of patients without recurrence of disease.
Phase 2: Nature, incidence, relatedness, and severity of treatment emergent adverse events (as assessed by CTCAE v5.0)
The type, incidence, relatedness and severity of treatment emergent adverse events of EG-70 as assessed by NCI-CTCAE V5.0 will be monitored.
Phase 1: The number of patients who experience a DLT through the end of Cycle 1
To identify the number of patients who experience a DLT through the end of Cycle 1
Phase 1: CR rate to EG-70 by cystoscopy at approximately 12 weeks.
To evaluate preliminary efficacy of EG-70 by 12 weeks via cystoscopy
Phase 2: Duration of response of the responding patients
Durability will be measured by determining the number of patients without recurrence of high-grade disease.
Phase 2: Progression-free survival (PFS)
To evaluate disease-free survival rate
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