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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT04752722Sponsor: enGene, Inc.Last updated: 2026-04-30

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

Sex: AllAge: 18 Years and olderHealthy 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: 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.

Study locations (49)

The University of Alabama at Birmingham Clinical Research Unit (CRU)

Birmingham, Alabama, 35249

Recruiting

Mayo Clinic

Scottsdale, Arizona, 85259

Recruiting

Urological Associates of South Arizona

Tucson, Arizona, 85715

Completed

Arkansas Urology

Little Rock, Arkansas, 72211

Recruiting

University of California - Irvine Medical Center

Irvine, California, 92697

Recruiting
Edward Uchio · Contact

UC San Diego Moores Cancer Center

La Jolla, California, 92037

Recruiting
Salmasi · Contact

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033

Recruiting

Tower Urology

Los Angeles, California, 90048

Recruiting

Om Research

San Diego, California, 92123

Recruiting
Alanna Gavriushina · Contact
Katayune Golshan · Contact

Colorado Clinical Research

Lakewood, Colorado, 80228

Recruiting

The George Washington Medical Faculty Associates

Washington D.C., District of Columbia, 20037

Recruiting
Michael Whalen · Contact

University of Florida

Jacksonville, Florida, 32209

Recruiting
Kethandapatti Balaji · Contact

Sylvester Comprehensive Cancer Center / University of Miami Hospital and Clinics

Miami, Florida, 33136

Recruiting

Emory University

Atlanta, Georgia, 30322

Recruiting
Shreyas Joshi · Contact

Rush University Medical Center

Chicago, Illinois, 60607

Recruiting

Urology of Indiana

Greenwood, Indiana, 46143

Recruiting

University of Kansas Medical Center

Kansas City, Kansas, 66160

Recruiting
Faith Rahman · Contact
Laura Mitchell · Contact

John Hopkins Hospital

Baltimore, Maryland, 21287

Recruiting

Chesapeake Urology Research Associates

Hanover, Maryland, 21076

Recruiting
Rian Dickstein · Contact

Brigham and Women's Hospital

Boston, Massachusetts, 45227

Recruiting
Mark Preston · Contact

Henry Ford Health System

Detroit, Michigan, 48202

Recruiting
Johar Raza, MD · Contact

Corewell Health Medical Group and Spectrum Health Hospitals

Grand Rapids, Michigan, 49503

Recruiting
Conrad Tobert · Contact

University of Minnesota

Minneapolis, Minnesota, 55455

Recruiting
Marissa Twedt · Contact
Joseph Zabell · Contact

Mayo Clinic

Rochester, Minnesota, 55905

Recruiting
Shah · Contact

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901

Recruiting
Packiam · Contact

New Jersey Urology, LLC

Voorhees Township, New Jersey, 08043

Recruiting
Gordon Brown · Contact

Albany Medical College

Albany, New York, 12208

Recruiting

Mount Sinai Medical Center

New Haven, New York, 10029

Recruiting
John Sfakianos · Contact

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016

Completed

Associated Medical Professionals of NY,

Syracuse, New York, 13210

Recruiting

UNC Chapel Hill Hospital

Chapel Hill, North Carolina, 27514

Recruiting

Duke Health - Duke Cancer Center

Durham, North Carolina, 27710

Recruiting

Associated Urologists of North Carolina

Raleigh, North Carolina, 27612

Recruiting
Mark Jalkut · Contact

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219

Recruiting
Mohammed Kamel · Contact

Central Ohio Urology Group

Gahanna, Ohio, 43230

Recruiting

Clinical Research Solutions - Helios Clinical Research

Middleburg Heights, Ohio, 44130

Recruiting

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239

Recruiting

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107

Recruiting

Carolina Urologic Research Center, LLC

Myrtle Beach, South Carolina, 29572

Recruiting

Urology Associates, P.C.

Nashville, Tennessee, 37209

Recruiting
Jayram · Contact

Vanderbilt Univerity Medical Center

Nashville, Tennessee, 37232

Recruiting
Chang · Contact

Urology Austin

Austin, Texas, 78745

Recruiting

UT Southwestern Medical Center

Dallas, Texas, 75390

Recruiting

Houston Metro Urology

Houston, Texas, 77027

Recruiting
Gelpi-Hammerschmidt · Contact

Houston Methodist Hospital - Department of Urology

Houston, Texas, 77030

Recruiting

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Ashish Kamat, MD · Contact

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112

Recruiting

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903

Recruiting
Christine Ibilibor · Contact

Froedtert Hospital / Medical College of Wisconsin

Milwaukee, Wisconsin, 52336

Recruiting
Scott Johnson · Contact