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Trial record 1 of 1 for:    nct04752722
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EG-70 in NMIBC Patients Who Are BCG-Unresponsive and High-Risk NMIBC Patients Who Have Been Incompletely Treated With BCG or Are BCG-Naïve (LEGEND STUDY)

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ClinicalTrials.gov Identifier: NCT04752722
Recruitment Status : Recruiting
First Posted : February 12, 2021
Last Update Posted : May 13, 2022
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 May 13, 2022
Actual Study Start Date  ICMJE April 22, 2021
Estimated Primary Completion Date July 2024   (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: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE EG-70 in NMIBC Patients Who Are BCG-Unresponsive and High-Risk NMIBC Patients Who Have Been Incompletely Treated With BCG or Are BCG-Naïve (LEGEND STUDY)
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 open-label, multicenter study will evaluate the safety and efficacy of intravesical administration of EG-70 and its effect on bladder tumors in patients with NMIBC who have failed BCG therapy and are recommended for radical cystectomy or high-risk NMIBC patients who are BCG-naïve or have received incomplete BCG treatment. This study study consists of two phases, a dose-escalation Phase (Phase 1) to establish safety and recommended phase 2 dose (RP2D), followed by a Phase 2 efficacy study at the RP2D to establish efficacy. 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).
Detailed Description EG-70 is a novel non-viral gene therapy. EG-70 is designed to elicit a local immune response following delivery of gene therapies to mucosal tissues, such as 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.
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
Intervention  ICMJE
  • Drug: EG-70
    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
    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
  • 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
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 February 2026
Estimated Primary Completion Date July 2024   (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 resected papillary tumors who are indicated for, ineligible for, or have elected not to undergo cystectomy:

    1. persistent high-grade disease (Ta, T1, or Tis) after receiving at least one induction course of intravesical BCG (at least 5 of 6 induction doses) or recurrence after 12 months of receiving at least one induction course of intravesical BCG (at least 5 of 6 induction doses), or
    2. T1 high grade disease residual at the first evaluation following induction BCG (at least 5 of 6 doses).

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

  2. NMIBC with CIS with or without resected papillary tumors who are indicated for, ineligible for, or have elected not to undergo cystectomy:

    1. persistent high-grade disease (Ta, T1, or Tis) or recurrence within 6 months of receiving at least 1 dose, but not the full course, of intravesical BCG, or
    2. high-grade disease (Ta, T1, or Tis) who have not yet received any treatment with BCG, or
    3. T1 high grade disease residual at the first evaluation following incomplete treatment with BCG
  3. Patients who have previously been treated with at least one dose of intravesical chemotherapy at TURBT are eligible for inclusion one month post-treatment.

    All Patients:

  4. 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).
  5. Male or non-pregnant, non-lactating female, 18 years or older.
  6. Women of childbearing potential must have a negative pregnancy test at Screening. A female patient is considered to be of child-producing potential unless she:

    1. has had a hysterectomy or bilateral oophorectomy or
    2. is age ≥ 60 years and is amenorrhoeic or
    3. is age < 60 years and has been amenorrhoeic for ≥ 12 months (including no irregular menses or spotting) in the absence of any medication which induces a menopausal state and has documented ovarian failure by serum oestradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range).
  7. All patients of childbearing potential must be willing to consent to using effective double-barrier contraception, i.e., intrauterine device, birth control pills, depo-provera, and condoms while on treatment and for 3 months after their participation in the study ends.
  8. Performance Status: Eastern Cooperative Oncology Group (ECOG) 0, 1, and 2.
  9. Hematologic inclusion within 2 weeks of start of treatment:

    1. Absolute neutrophil count >1,500/mm3.
    2. Hemoglobin >9.0 g/dl.
    3. Platelet count >100,000/mm3.
  10. Hepatic inclusion within 2 weeks of Day 1:

    1. Total bilirubin must be ≤1.5 x the upper limit of normal (ULN).
    2. Adequate renal function with creatinine clearance >30 mL/min (measured using Cockcroft-Gault equation or the estimated glomerular filtration rate from the Modification of Diet in Renal Disease Study).
    3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN for the institution, alkaline phosphatase ≤2.5 x ULN for the institution, unless bone metastasis is present in the absence of liver metastasis.
  11. Prothrombin time and partial thromboplastin time within the normal limits at Screening.
  12. Must have satisfactory bladder function with ability to retain study drug for a minimum of 60 minutes.
  13. Patient or legally authorized representative (LAR) must be willing and able to comply with all protocol requirements.
  14. Patient or LAR must be willing and able to give informed consent and any authorizations required by local law for participation in the study.

Exclusion Criteria:

  1. Any other malignancy diagnosed within 1 year of study entry (except basal or squamous cell skin cancers or noninvasive cancer of the cervix) is excluded.
  2. Concurrent treatment with any chemotherapeutic agent.
  3. Treatment with pembrolizumab within 30 days (Phase 1) or 3 months (Phase 2) prior to Screening.
  4. Treatment with last therapeutic agent within 30 days of Screening (Phase 1 and Phase 2) or treatment with an investigational checkpoint inhibitor within 3 months of Screening (Phase 2 only).
  5. History of vesicoureteral reflux or an indwelling urinary stent.
  6. Participation in any other research protocol involving administration of an investigational agent within 1 month prior to Day 1.
  7. History of external beam radiation to the pelvis at any time or prostate brachytherapy within the last 12 months.
  8. History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
  9. Evidence of metastatic disease.
  10. History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.
  11. History of interstitial cystitis.
  12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  13. Known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.
  14. Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
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: Bao Le 5143324888 clinicaltrials@engene.com
Contact: Loraine Warner 5143324888 clinicaltrials@engene.com
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 Not Provided
PRS Account enGene, Inc.
Verification Date March 2022

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