LEGEND Study: EG-70 in NMIBC Patients BCG-Unresponsive and High-Risk NMIBC Incompletely Treated With BCG or BCG-Naïve
- Conditions
- Superficial Bladder CancerNon-muscle Invasive Bladder Cancer With Carcinoma in Situ
- Interventions
- Drug: EG-70 (phase 1)Drug: EG-70 (phase 2)
- Registration Number
- NCT04752722
- Lead Sponsor
- enGene, Inc.
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 350
BCG-unresponsive Patients:
-
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:
-
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:
-
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.
-
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.
-
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.
-
Performance Status: Eastern Cooperative Oncology Group 0, 1, and 2.
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Hematologic inclusion: a. Absolute neutrophil count >1,500/mm3. b. Hemoglobin >9.0 g/dL. c. Platelet count >100,000/mm3.
-
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.
-
Adequate renal function with creatinine clearance >30 mL/min
-
Prothrombin time and partial thromboplastin time ≤1.25 x ULN or within the therapeutic range if on anticoagulation therapy.
-
Must have satisfactory bladder function with ability to retain study drug for 60 minutes.
- 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).
- Patients who have received systemic immunosuppressive medication including high-dose corticosteroids.
- History of severe asthma or other respiratory diseases.
- History of unresolved vesicoureteral reflux or an indwelling urinary stent.
- History of unresolved hydronephrosis due to ureteral obstruction.
- 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.
- History of external beam radiation to the pelvis or prostate brachytherapy within the last 12 months.
- History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
- Evidence of metastatic disease.
- History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.
- Active interstitial cystitis on cystoscopy or biopsy.
- Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
- Known human immunodeficiency virus, Hepatitis B, or Hepatitis C infection.
- Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
- Hypersensitivity to any of the excipients of the study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 EG-70 (phase 1) Dose escalation phase Phase 2 EG-70 (phase 2) Cohort 1: Recommended Phase 2 dose (RP2D) with eligible BCG-unresponsive NMIBC patients with CIS, up to 4 cycles of treatment with EG-70 Cohorts 2A, 2B and 3: RP2D with eligible high-risk NMIBC patients with CIS who are BCG-naïve, BCG-exposed (incompletely treated with BCG) or BCG-unresponsive HG Ta/T1 papillary disease without CIS
- Primary Outcome Measures
Name Time Method 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: 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.
Phase 2: Percentage of patients with cystoscopic CR at 48 weeks, based on exam, urine cytology and appropriate biopsies. Approximately 48 weeks Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease.
- Secondary Outcome Measures
Name Time Method Phase 2: Progression-free survival (PFS) Approximately 3 years To evaluate disease-free survival rate
Phase 1: CR rate to EG-70 by cystoscopy at approximately 12 weeks. Approximately 12 weeks To evaluate preliminary efficacy of EG-70 by 12 weeks via cystoscopy
Phase 2: CR rate at 12, 24, 36, and 96 weeks Approximately 12, 24, 36, and 96 weeks To further evaluate CR at the efficacy analysis following each cycle.
Phase 2: Duration of response of the responding patients Approximately 3 years Durability will be measured by determining the number of patients without recurrence of high-grade disease.
Phase 2: Quality of Life Assessment 24 weeks Health-related quality of life
Phase 1: The number of patients who experience a DLT through the end of Cycle 1 Approximately 12 Weeks To identify the number of patients who experience a DLT through the end of Cycle 1
Trial Locations
- Locations (75)
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Arkansas Urology
🇺🇸Little Rock, Arkansas, United States
Colorado Clinical Research
🇺🇸Lakewood, Colorado, United States
Urology of Indiana
🇺🇸Greenwood, Indiana, United States
Associated Medical Professionals of NY,
🇺🇸Syracuse, New York, United States
Central Ohio Urology Group
🇺🇸Gahanna, Ohio, United States
The University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
Urology Austin
🇺🇸Austin, Texas, United States
Sydney Adventist Hospital
🇦🇺Wahroonga, New South Wales, Australia
Prostate Cancer Centre
🇨🇦Calgary, Alberta, Canada
Vancouver Prostate Centre
🇨🇦Vancouver, British Columbia, Canada
Urologie Neandertal Mettmann
🇩🇪Mettmann, Germany
Clinic Unit of Urology, IRCCS Ospedale San Raffaele
🇮🇹Milano, MI, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
🇮🇹Napoli, Italy
Azienda Ospedaliero-Universitaria Sant'Andrea
🇮🇹Rome, Italy
Seoul National University Bundang Hospital
🇰🇷Seongnam, Gyunggi-do, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Jeollanam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Marqués de Valdecilla,
🇪🇸Santander, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Chi Mei Medical Center
🇨🇳Tainan city, Taiwan
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Urological Associates of South Arizona
🇺🇸Tucson, Arizona, United States
University of California - Irvine Medical Center
🇺🇸Irvine, California, United States
UC San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
Urology Group of Southern California / American Institute of Research
🇺🇸Los Angeles, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Tower Urology
🇺🇸Los Angeles, California, United States
Genesis Research
🇺🇸San Diego, California, United States
The George Washington Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
University of Florida
🇺🇸Jacksonville, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Chesapeake Urology Research Associates
🇺🇸Hanover, Maryland, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Corewell Health Medical Group and Spectrum Health Hospitals
🇺🇸Grand Rapids, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
New Jersey Urology, LLC
🇺🇸Voorhees, New Jersey, United States
Albany Medical College
🇺🇸Albany, New York, United States
Mount Sinai Medical Center
🇺🇸New Haven, New York, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
🇺🇸New York, New York, United States
UNC Chapel Hill Hospital
🇺🇸Chapel Hill, North Carolina, United States
Associated Urologists of North Carolina
🇺🇸Raleigh, North Carolina, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Clinical Research Solutions - Helios Clinical Research
🇺🇸Middleburg Heights, Ohio, United States
Oregon Health & Science University (OHSU)
🇺🇸Portland, Oregon, United States
Carolina Urologic Research Center, LLC
🇺🇸Myrtle Beach, South Carolina, United States
Urology Associates, P.C.
🇺🇸Nashville, Tennessee, United States
Vanderbilt Univerity Medical Center
🇺🇸Nashville, Tennessee, United States
Urology Austin, PLLC
🇺🇸Austin, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Houston Metro Urology
🇺🇸Houston, Texas, United States
Houston Methodist Hospital - Department of Urology
🇺🇸Houston, Texas, United States
University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Virginia Comprehensive Cancer Center
🇺🇸Charlottesville, Virginia, United States
Froedtert Hospital / Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Icon Cancer Center Windsor Gardens
🇦🇺Windsor Gardens, South Australia, Australia
Nova Scotia Health Authority
🇨🇦Halifax, Nova Scotia, Canada
McGill University Health Center - Glen site
🇨🇦Montréal, Quebec, Canada
CHUM Centre Hospitalier de l Universite de Montreal
🇨🇦Montréal, Quebec, Canada
CHU Bordeaux Pellegrin
🇫🇷Bordeaux, France
CHU de Lille
🇫🇷Lille, France
Urologicum Duisburg
🇩🇪Duisburg, Germany
Fundacio Puigvert
🇪🇸Barcelona, Spain
Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Infanta Sofia
🇪🇸Madrid, Spain