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History of Changes for Study: NCT04752722
EG-70 in Patients With BCG-Unresponsive NMIBC (LEGEND STUDY)
Latest version (submitted May 11, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 11, 2021 None (earliest Version on record)
2 March 15, 2021 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 June 7, 2021 Study Status and Contacts/Locations
4 August 13, 2021 Study Status and Contacts/Locations
5 August 31, 2021 Contacts/Locations and Study Status
6 September 14, 2021 Contacts/Locations and Study Status
7 October 27, 2021 Arms and Interventions, Study Status, Study Identification, Eligibility, Study Design, Conditions and Study Description
8 January 21, 2022 Contacts/Locations and Study Status
9 March 6, 2022 Study Status and Contacts/Locations
10 May 11, 2022 Contacts/Locations and Study Status
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Study NCT04752722
Submitted Date:  February 11, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: EG-70-101
Brief Title: EG-70 in Patients With BCG-Unresponsive NMIBC (LEGEND STUDY)
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)
Secondary IDs:
Open or close this module Study Status
Record Verification: February 2021
Overall Status: Not yet recruiting
Study Start: March 2021
Primary Completion: July 2024 [Anticipated]
Study Completion: February 2026 [Anticipated]
First Submitted: February 4, 2021
First Submitted that
Met QC Criteria:
February 11, 2021
First Posted: February 12, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
February 11, 2021
Last Update Posted: February 12, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: enGene, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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. This study study consists of two parts, 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.
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.
Open or close this module Conditions
Conditions: Superficial Bladder Cancer
Keywords: Non-muscle invasive bladder cancer (NMIBC)
Bacillus calmette- guerin (BCG) failure
BCG unresponsive
NMIBC
Bladder Cancer
LEGEND Study
EG-70
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 124 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Phase 1
Dose escalation phase
Drug: EG-70
Patients will receive one cycle 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 is defined by 2 intravesical administrations separated by 1 week, and followed by another 10 weeks (1 cycle lasts approximately 12 weeks).
Other Names:
  • Phase 1
Experimental: Phase 2
Recommended Phase 2 dose, up to 4 cycles of treatment with EG-70
Drug: EG-70
Patients will receive up to 4 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 is defined by 2 intravesical administrations separated by 1 week, and followed by another 10 weeks (1 cycle lasts approximately 12 weeks).
Other Names:
  • Phase 2
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
2. 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.
3. 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.
Secondary Outcome Measures:
1. 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
2. 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
3. Phase 2: Progression-free survival (PFS)
[ Time Frame: Approximately 4 years ]

To evaluate disease-free survival rate.
4. 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.
5. 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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  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) or recurrence within 6 months of receiving at least 2 courses of intravesical BCG (at least 5 of 6 induction doses and at least 2 of 3 maintenance doses).
    2. T1 high grade disease residual at the first evaluation following induction BCG (at least 5 of 6 doses).
  2. 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).
  3. Male or non-pregnant, non-lactating female, 18 years or older.
  4. 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).
  5. 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.
  6. Performance Status: Eastern Cooperative Oncology Group (ECOG) 0, 1, and 2.
  7. 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.
  8. 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.
  9. Prothrombin time and partial thromboplastin time within the normal limits at Screening.
  10. Must have satisfactory bladder function with ability to retain study drug for a minimum of 60 minutes.
  11. Must be willing and able to comply with all protocol requirements.
  12. 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. Women who are pregnant or lactating.
  6. History of vesicoureteral reflux or an indwelling urinary stent.
  7. Participation in any other research protocol involving administration of an investigational agent within 1 month prior to Day 1.
  8. History of radiation to the pelvis.
  9. History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
  10. Evidence of metastatic disease.
  11. History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.
  12. History of interstitial cystitis.
  13. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  14. Known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.
  15. Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
Open or close this module Contacts/Locations
Central Contact Person: Bao Le
Telephone: 5143324888
Email: clinicaltrials@engene.com
Central Contact Backup: Loraine Warner
Telephone: 5143324888
Email: clinicaltrials@engene.com
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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