A Phase 1/2 Study of EG-70 as an Intravesical Administration to Patients With BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) and High-Risk NMIBC Patients Who Are BCG Naïve or Received Incomplete BCG Treatment
Summary
This study will evaluate the safety and efficacy of intravesical administration of 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 patients with NMIBC with Cis who are BCG-naïve or inadequately treated.
Detailed description
EG-70 is a novel non-viral gene therapy. EG-70 is designed to elicit a local immune response following delivery of the study gene therapy to the bladder urothelium. This approach of local administration through bladder instillation has the potential to induce a potent immune response exclusively at the site of the tumor, resulting in greater therapeutic benefit while reducing undesirable systemic toxicity. Eligible BCG-unresponsive NMIBC patients will be enrolled in Phase 1, and Cohort 1 of Phase 2. Eligible high-risk NMIBC patients will be enrolled starting in Phase 2 in separate single are cohorts include: BCG-naïve patients or BCG-exposed (incompletely treated) patients with Carcinoma in situ (CIS), and BCG-unresponsive HG Ta/T1 papillary disease without CIS. Patients will be treated for up to four 12-week cycles of study drug instillation doses and assessments with follow up assessments. Patients with complete response following the four 12-week cycles will enter up to 4 maintenance treatment cycles, and those remaining in complete response will enter another 4 maintenance treatment cycles or follow up assessments.
Arms & interventions
- DrugEG-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.
- DrugEG-70 (phase 2)
Patients will receive during Treatment Period, 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.
Outcome measures
Primary
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.
Time frame: Approximately 2 years
Phase 2: Percentage of patients with cystoscopic CR at 48 weeks, based on exam, urine cytology and appropriate biopsies.
Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease.
Time frame: Approximately 48 weeks
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.
Time frame: Approximately 3 years
Secondary
Phase 1: The number of patients who experience a DLT through the end of Cycle 1
Time frame: Approximately 12 Weeks
Phase 1: CR rate to EG-70 by cystoscopy at approximately 12 weeks.
Time frame: Approximately 12 weeks
Phase 2: Progression-free survival (PFS)
Time frame: Approximately 3 years
Phase 2: CR rate at 12, 24, 36, and 96 weeks
Time frame: Approximately 12, 24, 36, and 96 weeks
Phase 2: Duration of response of the responding patients
Time frame: Approximately 3 years
Phase 2: Quality of Life Assessment
Time frame: 24 weeks
Eligibility criteria
Study locations (49)
The University of Alabama at Birmingham Clinical Research Unit (CRU)
Birmingham, Alabama, 35249
Mayo Clinic
Scottsdale, Arizona, 85259
Urological Associates of South Arizona
Tucson, Arizona, 85715
Arkansas Urology
Little Rock, Arkansas, 72211
University of California - Irvine Medical Center
Irvine, California, 92697
UC San Diego Moores Cancer Center
La Jolla, California, 92037
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Tower Urology
Los Angeles, California, 90048
Om Research
San Diego, California, 92123
Colorado Clinical Research
Lakewood, Colorado, 80228
The George Washington Medical Faculty Associates
Washington D.C., District of Columbia, 20037
University of Florida
Jacksonville, Florida, 32209
Sylvester Comprehensive Cancer Center / University of Miami Hospital and Clinics
Miami, Florida, 33136
Emory University
Atlanta, Georgia, 30322
Rush University Medical Center
Chicago, Illinois, 60607
Urology of Indiana
Greenwood, Indiana, 46143
University of Kansas Medical Center
Kansas City, Kansas, 66160
John Hopkins Hospital
Baltimore, Maryland, 21287
Chesapeake Urology Research Associates
Hanover, Maryland, 21076
Brigham and Women's Hospital
Boston, Massachusetts, 45227
Henry Ford Health System
Detroit, Michigan, 48202
Corewell Health Medical Group and Spectrum Health Hospitals
Grand Rapids, Michigan, 49503
University of Minnesota
Minneapolis, Minnesota, 55455
Mayo Clinic
Rochester, Minnesota, 55905
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
New Jersey Urology, LLC
Voorhees Township, New Jersey, 08043
Albany Medical College
Albany, New York, 12208
Mount Sinai Medical Center
New Haven, New York, 10029
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
Associated Medical Professionals of NY,
Syracuse, New York, 13210
UNC Chapel Hill Hospital
Chapel Hill, North Carolina, 27514
Duke Health - Duke Cancer Center
Durham, North Carolina, 27710
Associated Urologists of North Carolina
Raleigh, North Carolina, 27612
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
Central Ohio Urology Group
Gahanna, Ohio, 43230
Clinical Research Solutions - Helios Clinical Research
Middleburg Heights, Ohio, 44130
Oregon Health & Science University (OHSU)
Portland, Oregon, 97239
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
Carolina Urologic Research Center, LLC
Myrtle Beach, South Carolina, 29572
Urology Associates, P.C.
Nashville, Tennessee, 37209
Vanderbilt Univerity Medical Center
Nashville, Tennessee, 37232
Urology Austin
Austin, Texas, 78745
UT Southwestern Medical Center
Dallas, Texas, 75390
Houston Metro Urology
Houston, Texas, 77027
Houston Methodist Hospital - Department of Urology
Houston, Texas, 77030
University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
University of Virginia Comprehensive Cancer Center
Charlottesville, Virginia, 22903
Froedtert Hospital / Medical College of Wisconsin
Milwaukee, Wisconsin, 52336