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

March 26, 2024 updated by: enGene, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 who have been incompletely treated or are BCG-naïve will be enrolled starting in Phase 2 in a separate single-arm cohort (Cohort 2).

Patients will be treated for up to four 12-week cycles of study drug instillation doses and assessments with follow up assessments.

Study Type

Interventional

Enrollment (Estimated)

222

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Chris Tosone

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85715
        • Recruiting
        • Urological Associates of South Arizona
        • Contact:
    • California
      • Irvine, California, United States, 92697
        • Recruiting
        • University of California - Irvine Medical Center
        • Contact:
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC/Norris Comprehensive Cancer Center
        • Contact:
      • Los Angeles, California, United States, 90048
      • Los Angeles, California, United States, 90017
        • Withdrawn
        • Urology Group of Southern California / American Institute of Research
      • San Diego, California, United States, 92123
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • Recruiting
        • The George Washington Medical Faculty Associates
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32209
        • Recruiting
        • University of Florida
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30322
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center
        • Contact:
        • Contact:
    • Maryland
      • Hanover, Maryland, United States, 21076
        • Recruiting
        • Chesapeake Urology Research Associates
        • Contact:
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health System
        • Contact:
      • Grand Rapids, Michigan, United States, 49503
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
    • New Jersey
      • Voorhees, New Jersey, United States, 08043
    • New York
      • New Haven, New York, United States, 10029
      • New York, New York, United States, 10016
        • Completed
        • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
      • Raleigh, North Carolina, United States, 27612
        • Recruiting
        • Associated Urologists of North Carolina
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Medical Center
        • Contact:
      • Middleburg Heights, Ohio, United States, 44130
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health & Science University (OHSU)
        • Contact:
    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Recruiting
        • Carolina Urologic Research Center, LLC
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas - MD Anderson Cancer Center
        • Contact:
      • Houston, Texas, United States, 77030
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 52336
        • Recruiting
        • Froedtert Hospital / Medical College of Wisconsin
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 1) persistent disease within 12 months of treatment or 2) a recurrence within 6 months of completion of adequate BCG therapy, 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

    BCG-Naïve or BCG-incompletely treated Patients (Phase 2 Only):

  2. 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: a) incomplete BCG (at least 1 dose) treatment or b) no treatment with BCG but who 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 indicated by pathology

    All Patients:

  3. Patients who have previously been treated with an investigational or approved checkpoint inhibitor (e.g., pembrolizumab) 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 effective double-barrier contraception and for 3 months (or longer in accordance with local regulatory requirements) after their participation in the study ends. 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, Screening biopsy must be considered adequate (contain the muscularis layer).
  8. Performance Status: Eastern Cooperative Oncology Group 0, 1, and 2.

  9. Hematologic inclusion:

    1. Absolute neutrophil count >1,500/mm3.
    2. Hemoglobin >9.0 g/dL.
    3. Platelet count >100,000/mm3.

  10. Hepatic inclusion:

    1. Total bilirubin must be ≤1.5 x the upper limit of normal (ULN).
    2. 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 a minimum of 60 minutes.
  14. Patient or legally authorized representative must be willing and able to comply with all protocol requirements.
  15. Must be willing and able to give informed consent.

Exclusion Criteria:

  1. Any malignancy (other than NMIBC) diagnosed within 1 year of study entry (except basal or squamous cell skin cancers or noninvasive cancer of the cervix) ), or any malignancy that has required therapy for active disease within the last 12 months.
  2. Concurrent treatment with any chemotherapeutic agent.
  3. History of partial cystectomy.
  4. Treatment with pembrolizumab within 30 days (Phase 1) or 3 months (Phase 2) prior to Screening.
  5. Treatment with last therapeutic agent (including intravesical chemotherapy post-TURBT) within 30 days of Screening.
  6. Evidence of persistent or ongoing renal failure.
  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 at any time 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. Consideration by the Investigator that the patient is an unsuitable candidate for the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1
Dose escalation phase
Drug: EG-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.
Other Names:
  • Phase 1
Experimental: Phase 2

Cohort 1: Recommended Phase 2 dose (RP2D) with eligible BCG-unresponsive NMIBC patients, up to 4 cycles of treatment with EG-70

Cohort 2: RP2D with eligible high-risk NMIBC patients who have been incompletely treated with BCG or are BCG-naïve
Drug: EG-70 (phase 2)
Cohort 1 and Cohort 2: Patients will receive 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.
Other Names:
  • Phase 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0.
Time Frame: 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.
Approximately 2 years
Phase 2: Percentage of patients with cystoscopic CR at 48 weeks, based on exam, urine cytology and appropriate biopsies.
Time Frame: Approximately 48 weeks
Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease.
Approximately 48 weeks
Phase 2: Nature, incidence, relatedness, and severity of treatment emergent adverse events (as assessed by CTCAE v5.0)
Time Frame: 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.
Approximately 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: CR rate to EG-70 by cystoscopy at approximately 12 weeks.
Time Frame: Approximately 12 weeks
To evaluate preliminary efficacy of EG-70 by 12 weeks via cystoscopy
Approximately 12 weeks
Phase 2: CR rate at 12, 24, 36, and 96 weeks
Time Frame: Approximately 12, 24, 36, and 96 weeks
To further evaluate CR at the efficacy analysis following each cycle.
Approximately 12, 24, 36, and 96 weeks
Phase 2: Duration of response of the responding patients
Time Frame: Approximately 3 years
Durability will be measured by determining the number of patients without recurrence of high-grade disease.
Approximately 3 years
Phase 1: The number of patients who experience a DLT through the end of Cycle 1
Time Frame: Approximately 12 Weeks
To identify the number of patients who experience a DLT through the end of Cycle 1
Approximately 12 Weeks
Phase 2: Progression-free survival (PFS)
Time Frame: Approximately 3 years
To evaluate disease-free survival rate
Approximately 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

enGene, Inc.

Investigators

  • Study Director: Christine Tosone, Ms, RAC, enGene, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 22, 2021

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

February 4, 2021

First Submitted That Met QC Criteria

February 11, 2021

First Posted (Actual)

February 12, 2021

Study Record Updates

Last Update Posted (Actual)

March 28, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EG-70-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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