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

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ClinicalTrials.gov Identifier: NCT04752722
Recruitment Status : Recruiting
First Posted : February 12, 2021
Last Update Posted : June 20, 2024
Sponsor:
Information provided by (Responsible Party):
enGene, Inc.

Tracking Information
First Submitted Date  ICMJE February 4, 2021
First Posted Date  ICMJE February 12, 2021
Last Update Posted Date June 20, 2024
Actual Study Start Date  ICMJE April 22, 2021
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2021)
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2024)
  • 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
  • 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
  • Phase 2: Progression-free survival (PFS) [ Time Frame: Approximately 3 years ]
    To evaluate disease-free survival rate
  • 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.
  • 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.
  • Phase 2: Quality of Life Assessment [ Time Frame: 24 weeks ]
    Health-related quality of life
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2021)
  • Phase 1: The number of patients who experience a DLT through the end of Cycle 1 [ Time Frame: Approximately 1 year ]
    To identify the number of patients who experience a DLT through the end of Cycle 1
  • 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
  • Phase 2: Progression-free survival (PFS) [ Time Frame: Approximately 4 years ]
    To evaluate disease-free survival rate.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE LEGEND Study: EG-70 in NMIBC Patients BCG-Unresponsive and High-Risk NMIBC Incompletely Treated With BCG or BCG-Naïve
Official Title  ICMJE 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
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 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Superficial Bladder Cancer
  • Non-muscle Invasive Bladder Cancer With Carcinoma in Situ
Intervention  ICMJE
  • 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 Name: Phase 1
  • 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 Name: Phase 2
Study Arms  ICMJE
  • Experimental: Phase 1
    Dose escalation phase
    Intervention: Drug: EG-70 (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

    Intervention: Drug: EG-70 (phase 2)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 27, 2021)
222
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2021)
124
Estimated Study Completion Date  ICMJE May 2027
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 highly effective birth control methods while on treatment 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. Hypersensitivity to any of the excipients of the study drug.
  19. Consideration by the Investigator that the patient is an unsuitable candidate for the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: enGene clinical trials +18572991097 clinicaltrials@engene.com
Contact: Chris Tosone
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04752722
Other Study ID Numbers  ICMJE EG-70-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party enGene, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE enGene, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Christine Tosone, Ms, RAC enGene, Inc.
PRS Account enGene, Inc.
Verification Date June 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP