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NCT04752722PHASE1, PHASE2Recruiting

LEGEND Study: EG-70 in NMIBC Patients BCG-Unresponsive and High-Risk NMIBC Incompletely Treated With BCG or BCG-Naïve

enGene, Inc.

Start Date

4/22/2021

Completion Date

11/30/2028

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.

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 with CIS patients will be enrolled in Phase 1, and Cohort 1 of Phase 2. Eligible high-risk NMIBC patients will be enrolled in Phase 2 into separate 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 four treatment cycles will enter up to 8 maintenance treatment cycles.

Eligibility Criteria

Age Range: 18 years to No maximum

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. Exclusionary for Bladder Rinse cohort: known allergy to polidocanol

Interventions

DRUG

EG-70 (phase 1)

DRUG

EG-70 (phase 2) Master Protocol

DRUG

Surfactant Bladder Pre-Rinse and EG-70 (Substudy)

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Conditions

Superficial Bladder CancerNon-muscle Invasive Bladder Cancer With Carcinoma in Situ

Locations

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

Birmingham, Alabama 35249

United States

Mayo Clinic

Scottsdale, Arizona 85259

United States

Urological Associates of South Arizona

Tucson, Arizona 85715

United States

Arkansas Urology

Little Rock, Arkansas 72211

United States

University of California - Irvine Medical Center

Irvine, California 92697

United States

UC San Diego Moores Cancer Center

La Jolla, California 92037

United States

USC/Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Tower Urology

Los Angeles, California 90048

United States

Om Research

San Diego, California 92123

United States

Colorado Clinical Research

Lakewood, Colorado 80228

United States

The George Washington Medical Faculty Associates

Washington D.C., District of Columbia 20037

United States

University of Florida

Jacksonville, Florida 32209

United States

Sylvester Comprehensive Cancer Center / University of Miami Hospital and Clinics

Miami, Florida 33136

United States

Emory University

Atlanta, Georgia 30322

United States

Georgia Cancer Center at Augusta University

Augusta, Georgia 30912

United States

Urology of Indiana

Greenwood, Indiana 46143

United States

University of Kansas Medical Center

Kansas City, Kansas 66160

United States

John Hopkins Hospital

Baltimore, Maryland 21287

United States

Chesapeake Urology Research Associates

Hanover, Maryland 21076

United States

Brigham and Women's Hospital

Boston, Massachusetts 45227

United States

Henry Ford Health System

Detroit, Michigan 48202

United States

Corewell Health Medical Group and Spectrum Health Hospitals

Grand Rapids, Michigan 49503

United States

University of Minnesota

Minneapolis, Minnesota 55455

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08901

United States

New Jersey Urology, LLC

Voorhees Township, New Jersey 08043

United States

Albany Medical College

Albany, New York 12208

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Mount Sinai Medical Center

New Haven, New York 10029

United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York 10016

United States

Associated Medical Professionals of NY,

Syracuse, New York 13210

United States

UNC Chapel Hill Hospital

Chapel Hill, North Carolina 27514

United States

Duke Health - Duke Cancer Center

Durham, North Carolina 27710

United States

Associated Urologists of North Carolina

Raleigh, North Carolina 27612

United States

University of Cincinnati Medical Center

Cincinnati, Ohio 45219

United States

Central Ohio Urology Group

Gahanna, Ohio 43230

United States

Clinical Research Solutions - Helios Clinical Research

Middleburg Heights, Ohio 44130

United States

Oregon Health & Science University (OHSU)

Portland, Oregon 97239

United States

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania 19107

United States

Carolina Urologic Research Center, LLC

Myrtle Beach, South Carolina 29572

United States

Urology Associates, P.C.

Nashville, Tennessee 37209

United States

Vanderbilt Univerity Medical Center

Nashville, Tennessee 37232

United States

Urology Austin

Austin, Texas 78745

United States

UT Southwestern Medical Center

Dallas, Texas 75390

United States

Houston Metro Urology

Houston, Texas 77027

United States

Houston Methodist Hospital - Department of Urology

Houston, Texas 77030

United States

University of Texas - MD Anderson Cancer Center

Houston, Texas 77030

United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah 84112

United States

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia 22903

United States

Froedtert Hospital / Medical College of Wisconsin

Milwaukee, Wisconsin 52336

United States

Sydney Adventist Hospital

Wahroonga, New South Wales 2076

Australia

Gold Coast University Hospital

Southport, Queensland 4215

Australia

Icon Cancer Center Windsor Gardens

Windsor Gardens, South Australia 5087

Australia

Prostate Cancer Centre

Calgary, Alberta T2V1P9

Canada

Vancouver Prostate Centre

Vancouver, British Columbia V5Z1M9

Canada

Nova Scotia Health Authority

Halifax, Nova Scotia B3H2Y9

Canada

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario M5G 2M9

Canada

McGill University Health Center - Glen site

Montreal, Quebec H4A3J1

Canada

CHUM Centre Hospitalier de l Universite de Montreal

Montreal, Quebec

Canada

CHU d'Angers

Angers, 49933

France

CHU Bordeaux Pellegrin

Bordeaux, 33076

France

lnstitut Bergonie 229 Cour de l'Argonne

Bordeaux, 33076

France

CHU de Lille

Lille, 59000

France

Hospices Civils de Lyon

Lyon, 69002

France

Hopital Bichat Claude-Bernard

Paris, 75018

France

CHU de Rauen- Hopital Charles Nicolle

Rouen, 76031

France

Klinik fur Urologie, Uro-Onkologie, spezielle urologische und Roboter-assistierte Chirurgie Universitatsklinikum Koln (AOR)

Cologne, 50937

Germany

Urologicum Duisburg

Duisburg, 47169

Germany

Universitaetsklinikum Erlangen

Erlangen, 91054

Germany

Urologie Neandertal Mettmann

Mettmann, 40822

Germany

Studienpraxis Urologie

Nürtingen, 72622

Germany

Universitaetsklinikum Tubingen

Tübingen, 72076

Germany

Clinic Unit of Urology, IRCCS Ospedale San Raffaele

Milan, MI 20132

Italy

Istituto Europeo di Oncologia

Milan, 20141

Italy

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, 80131

Italy

Fondazione Policlinico Universitario "A.Gemelli" IRCCS, Largo

Rome, 00168

Italy

Azienda Ospedaliero-Universitaria Sant'Andrea

Rome, 00189

Italy

UOC Urologia, IFO- lstituto Tumori "Regina Elena"

Rome, 53 00144

Italy

Ospedelae Molinette San Giovanni Battista Di Torino

Torino, 10126

Italy

Seoul National University Bundang Hospital

Seongnam, Gyunggi-do 13620

South Korea

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do 58128

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital, Yonsei University Health System

Seoul, 03722

South Korea

The Catholic University of Korea, Soul St. Mary's Hospital

Seoul, 06591

South Korea

IOB - Hospital Quironsalud Barcelona

Barbera Del Valles, 5-7

Spain

Fundacio Puigvert

Barcelona, 08025

Spain

Hospital Clinic Barcelona

Barcelona, 08036

Spain

Hospital Germans Trias i Pujol

Barcelona, 08916

Spain

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, 08907

Spain

Hospital General Universitario Gregorio Maranon

Madrid, 28007

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Universitario La Paz

Madrid, 28046

Spain

Hospital Quironsalud Madrid (Next Oncology)

Madrid, 28223

Spain

Hospital Universitario Infanta Sofia

Madrid, 28702

Spain

Hospital General Universitario Morales Meseguer

Murcia, 30008

Spain

Hospital Universitario Marqués de Valdecilla,

Santander, 39008

Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807

Taiwan

China Medical University Hospital

Taichung, 40447

Taiwan

Taichung Veterans General Hospital

Taichung, 40705

Taiwan

Chi Mei Medical Center

Tainan, 71004

Taiwan

National Taiwan University Hospital

Taipei, 100

Taiwan

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ

United Kingdom