EG-70 (phase 1): Patients 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: Under 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): Patients 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.
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
BCG-unresponsive Patients:
1. 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
Phase 2 Only:
2. BCG-Naïve or BCG-incompletely treated Patients with CIS or BCG-unresponsive, HG Ta/T1 papillary disease without CIS:
-NMIBC with current Cis of the bladder, with or without coexisting papillary Ta/T1 NMIBC tumor(s), who are ineligible for or have elected not to undergo cystectomy, where: either: cohort 2a) no treatment with BCG but may have previously been treated with at least 1 dose of intravesical chemotherapy following transurethral resection of bladder tumor (TURBT) and Cis must be documented or cohort 2b) indicated by pathology incomplete BCG treatment (at least 1 dose and less than the 5+2 doses required for adequate dosing per Cohort 1) or cohort 3) patients who are BCG-unresponsive following adequate treatment, with HG Ta/T1 papillary disease without CIS.
All Patients with High Grade NMIBC:
3. 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).
4. Male or non-pregnant, non-lactating female, 18 years or older.
5. Women of childbearing potential must have a negative pregnancy test at Screening.
6. Female patients of childbearing potential must be willing to consent to using highly effective birth control methods; Male patients are required to utilize a condom for the duration of the study treatment through 3 months post-dose.
7. In Phase 2, for patients with T1 lesions may be eligible after repeat TURBT if pathology shows non-invasive (Ta or less) or no disease.
8. Performance Status: Eastern Cooperative Oncology Group 0, 1, and 2.
9. Hematologic inclusion: a. Absolute neutrophil count \>1,500/mm3. b. Hemoglobin \>9.0 g/dL. c. Platelet count \>100,000/mm3.
10. Hepatic inclusion: a. Total bilirubin must be ≤1.5 x the upper limit of normal (ULN). b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤2.5 x ULN.
11. Adequate renal function with creatinine clearance \>30 mL/min
12. Prothrombin time and partial thromboplastin time ≤1.25 x ULN or within the therapeutic range if on anticoagulation therapy.
13. Must have satisfactory bladder function with ability to retain study drug for 60 minutes.
Exclusion Criteria:
1. Active malignancies (i.e., progressing or requiring treatment change in the last 24 months). Exceptions allowed under Sponsor review.
2. Concurrent treatment with any chemotherapeutic agent.
3. History of partial cystectomy.
4. Treatment with last therapeutic agent (including intravesical chemotherapy post-TURBT) within 30 days of Screening (prior to the screening biopsy).
5. Patients who have received systemic immunosuppressive medication including high-dose corticosteroids.
6. History of severe asthma or other respiratory diseases.
7. History of unresolved vesicoureteral reflux or an indwelling urinary stent.
8. History of unresolved hydronephrosis due to ureteral obstruction.
9. Participation in any other research protocol involving administration of an investigational agent within 30 Days prior to screening or any prior treatment of NMIBC with any investigational gene or immunotherapy agent.
10. History of external beam radiation to the pelvis or prostate brachytherapy within the last 12 months.
11. History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
12. Evidence of metastatic disease.
13. History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.
14. Active interstitial cystitis on cystoscopy or biopsy.
15. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
16. Known human immunodeficiency virus, Hepatitis B, or Hepatitis C infection.
17. Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
18. Hypersensitivity to any of the excipients of the study drug.
Exclusionary for Bladder Rinse cohorts: known allergy to polidocanol
Primary outcome measure(s)
Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0. — Approximately 2 years 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. — Approximately 24 weeks 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) — Approximately 3 years The type, incidence, relatedness and severity of treatment emergent adverse events of EG-70 as assessed by NCI-CTCAE V5.0 will be monitored.
Trial sites (102)
Facility
City
Region
Status
The University of Alabama at Birmingham Clinical Research Unit (CRU)
Birmingham
Alabama
Recruiting
Mayo Clinic
Scottsdale
Arizona
Recruiting
Urological Associates of South Arizona
Tucson
Arizona
Completed
Arkansas Urology
Little Rock
Arkansas
Recruiting
University of California - Irvine Medical Center
Irvine
California
Recruiting
UC San Diego Moores Cancer Center
La Jolla
California
Recruiting
USC/Norris Comprehensive Cancer Center
Los Angeles
California
Recruiting
Tower Urology
Los Angeles
California
Recruiting
Om Research
San Diego
California
Recruiting
Colorado Clinical Research
Lakewood
Colorado
Recruiting
The George Washington Medical Faculty Associates
Washington D.C.
District of Columbia
Recruiting
University of Florida
Jacksonville
Florida
Recruiting
Sylvester Comprehensive Cancer Center / University of Miami Hospital and Clinics
Miami
Florida
Recruiting
Emory University
Atlanta
Georgia
Recruiting
Georgia Cancer Center at Augusta University
Augusta
Georgia
Recruiting
Urology of Indiana
Greenwood
Indiana
Recruiting
University of Kansas Medical Center
Kansas City
Kansas
Recruiting
John Hopkins Hospital
Baltimore
Maryland
Recruiting
Chesapeake Urology Research Associates
Hanover
Maryland
Recruiting
Brigham and Women's Hospital
Boston
Massachusetts
Recruiting
Henry Ford Health System
Detroit
Michigan
Recruiting
Corewell Health Medical Group and Spectrum Health Hospitals
Grand Rapids
Michigan
Recruiting
University of Minnesota
Minneapolis
Minnesota
Recruiting
Mayo Clinic
Rochester
Minnesota
Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick
New Jersey
Recruiting
New Jersey Urology, LLC
Voorhees Township
New Jersey
Recruiting
Albany Medical College
Albany
New York
Recruiting
Roswell Park Cancer Institute
Buffalo
New York
Recruiting
Mount Sinai Medical Center
New Haven
New York
Recruiting
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York
New York
Completed
Associated Medical Professionals of NY,
Syracuse
New York
Recruiting
UNC Chapel Hill Hospital
Chapel Hill
North Carolina
Recruiting
Duke Health - Duke Cancer Center
Durham
North Carolina
Recruiting
Associated Urologists of North Carolina
Raleigh
North Carolina
Recruiting
University of Cincinnati Medical Center
Cincinnati
Ohio
Recruiting
Central Ohio Urology Group
Gahanna
Ohio
Recruiting
Clinical Research Solutions - Helios Clinical Research
Middleburg Heights
Ohio
Recruiting
Oregon Health & Science University (OHSU)
Portland
Oregon
Recruiting
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia
Pennsylvania
Recruiting
Carolina Urologic Research Center, LLC
Myrtle Beach
South Carolina
Recruiting
+ 62 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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