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)
Study Details
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 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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Phase 1 Dose escalation phase |
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 Names:
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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
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:
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Outcome Measures
Primary Outcome Measures
- Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0. [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. [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) [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
- Phase 1: The number of patients who experience a DLT through the end of Cycle 1 [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. [Approximately 12 weeks]
To evaluate preliminary efficacy of EG-70 by 12 weeks via cystoscopy
- Phase 2: Progression-free survival (PFS) [Approximately 4 years]
To evaluate disease-free survival rate.
- Phase 2: CR rate at 12, 24, 36, and 96 weeks [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 [Approximately 3 years]
Durability will be measured by determining the number of patients without recurrence of high-grade disease.
Eligibility Criteria
Criteria
Inclusion Criteria:
BCG-unresponsive Patients:
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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:
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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
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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):
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NMIBC with CIS with or without resected papillary tumors who are indicated for, ineligible for, or have elected not to undergo cystectomy:
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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
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high-grade disease (Ta, T1, or Tis) who have not yet received any treatment with BCG, or
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T1 high grade disease residual at the first evaluation following incomplete treatment with BCG
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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:
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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).
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Male or non-pregnant, non-lactating female, 18 years or older.
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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:
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has had a hysterectomy or bilateral oophorectomy or
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is age ≥ 60 years and is amenorrhoeic or
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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).
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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.
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Performance Status: Eastern Cooperative Oncology Group (ECOG) 0, 1, and 2.
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Hematologic inclusion within 2 weeks of start of treatment:
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Absolute neutrophil count >1,500/mm3.
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Hemoglobin >9.0 g/dl.
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Platelet count >100,000/mm3.
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Hepatic inclusion within 2 weeks of Day 1:
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Total bilirubin must be ≤1.5 x the upper limit of normal (ULN).
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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).
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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.
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Prothrombin time and partial thromboplastin time within the normal limits at Screening.
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Must have satisfactory bladder function with ability to retain study drug for a minimum of 60 minutes.
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Patient or legally authorized representative (LAR) must be willing and able to comply with all protocol requirements.
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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:
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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.
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Concurrent treatment with any chemotherapeutic agent.
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Treatment with pembrolizumab within 30 days (Phase 1) or 3 months (Phase 2) prior to Screening.
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Treatment with last therapeutic agent within 30 days of Screening (Phase 1 and Phase
- or treatment with an investigational checkpoint inhibitor within 3 months of Screening (Phase 2 only).
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History of vesicoureteral reflux or an indwelling urinary stent.
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Participation in any other research protocol involving administration of an investigational agent within 1 month prior to Day 1.
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History of external beam radiation to the pelvis at any time or prostate brachytherapy within the last 12 months.
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History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
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Evidence of metastatic disease.
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History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.
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History of interstitial cystitis.
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Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
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Known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.
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Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Urological Associates of South Arizona, PLLC | Tucson | Arizona | United States | 85715 |
2 | Urology Group of Southern California | Los Angeles | California | United States | 90017 |
3 | Tower Urology | Los Angeles | California | United States | 90048 |
4 | Emory University | Atlanta | Georgia | United States | 30322 |
5 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
6 | New Jersey Urology, LLC | Voorhees | New Jersey | United States | 08043 |
7 | Laura & Isaac Perlmutter Cancer Center at NYU Langone Health | New York | New York | United States | 10016 |
8 | UT Southwestern Medical Center | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- enGene, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EG-70-101