Clinical trial NCT04752722: LEGEND Study: EG-70 in NMIBC Patients BCG-Unresponsive and High-Risk NMIBC Incompletely Treated With BCG or BCG-Naïve
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Superficial Bladder Cancer
Non-muscle Invasive Bladder Cancer With Carcinoma in Situ
Keywords: Non-muscle invasive bladder cancer (NMIBC)
Bacillus calmette- guerin (BCG) failure
BCG unresponsive
NMIBC
Bladder Cancer
LEGEND Study
EG-70
High-risk NMIBC
BCG-naïve
Incomplete BCG treatment
Carcinoma in situ (Cis)
BCG-exposed
Lead sponsor: enGene, Inc.
Sponsor class: INDUSTRY
First posted: 2021-02-12
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0.
timeFrame: Approximately 2 years
measure: Phase 2: Percentage of patients with cystoscopic CR at 48 weeks, based on exam, urine cytology and appropriate biopsies.
timeFrame: Approximately 48 weeks
measure: Phase 2: Nature, incidence, relatedness, and severity of treatment emergent adverse events (as assessed by CTCAE v5.0)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Phase 1: The number of patients who experience a DLT through the end of Cycle 1
timeFrame: Approximately 12 Weeks
measure: Phase 1: CR rate to EG-70 by cystoscopy at approximately 12 weeks.
timeFrame: Approximately 12 weeks
measure: Phase 2: Progression-free survival (PFS)
timeFrame: Approximately 3 years
measure: Phase 2: CR rate at 12, 24, 36, and 96 weeks
timeFrame: Approximately 12, 24, 36, and 96 weeks
measure: Phase 2: Duration of response of the responding patients
timeFrame: Approximately 3 years
measure: Phase 2: Quality of Life Assessment
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: Urological Associates of South Arizona
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Irvine
country: United States
facility: University of California - Irvine Medical Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Urology Group of Southern California / American Institute of Research
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Tower Urology
state: California
city: San Diego
country: United States
facility: Genesis Research
state: California
city: Lakewood
country: United States
facility: Colorado Clinical Research
state: Colorado
city: Washington
country: United States
facility: The George Washington Medical Faculty Associates
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Greenwood
country: United States
facility: Urology of Indiana
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Hanover
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Medical Group and Spectrum Health Hospitals
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Voorhees
country: United States
facility: New Jersey Urology, LLC
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New Haven
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of NY,
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill Hospital
state: North Carolina
city: Raleigh
country: United States
facility: Associated Urologists of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Gahanna
country: United States
facility: Central Ohio Urology Group
state: Ohio
city: Middleburg Heights
country: United States
facility: Clinical Research Solutions - Helios Clinical Research
state: Ohio
city: Toledo
country: United States
facility: The University of Toledo Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center, LLC
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, P.C.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Univerity Medical Center
state: Tennessee
city: Austin
country: United States
facility: Urology Austin, PLLC
state: Texas
city: Austin
country: United States
facility: Urology Austin
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Metro Urology
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital - Department of Urology
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Comprehensive Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital / Medical College of Wisconsin
state: Wisconsin
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital
state: New South Wales
city: Windsor Gardens
country: Australia
facility: Icon Cancer Center Windsor Gardens
state: South Australia
city: Calgary
country: Canada
facility: Prostate Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Prostate Centre
state: British Columbia
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Montréal
country: Canada
facility: McGill University Health Center - Glen site
state: Quebec
city: Montréal
country: Canada
facility: CHUM Centre Hospitalier de l Universite de Montreal
state: Quebec
city: Bordeaux
country: France
facility: CHU Bordeaux Pellegrin
city: Lille
country: France
facility: CHU de Lille
city: Duisburg
country: Germany
facility: Urologicum Duisburg
city: Mettmann
country: Germany
facility: Urologie Neandertal Mettmann
city: Milano
country: Italy
facility: Clinic Unit of Urology, IRCCS Ospedale San Raffaele
state: MI
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario "A.Gemelli" IRCCS, Largo
city: Rome
country: Italy
facility: Azienda Ospedaliero-Universitaria Sant'Andrea
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyunggi-do
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Soul St. Mary's Hospital
city: Barberà Del Vallès
country: Spain
facility: IOB - Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Fundacio Puigvert
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Sofia
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla,
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan city
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: enGene, Inc.
name: Christine Tosone, Ms, RAC
role: STUDY_DIRECTOR
References: