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

Superficial Bladder Cancer Clinical Trial

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) and High-Risk NMIBC Patients Who Are BCG Naïve or Received Incomplete BCG Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04752722
• Other study ID #: EG-70-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 22, 2021
• Est. completion date: May 2027

Study information

• Verified date: June 2024
• Source: enGene, Inc.
• Contact: enGene clinical trials
• Phone: +18572991097
• Email: clinicaltrials[@]engene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 222
• Est. completion date: May 2027
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma in Situ
• Superficial Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	UNC Chapel Hill Hospital	Chapel Hill	North Carolina
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Corewell Health Medical Group and Spectrum Health Hospitals	Grand Rapids	Michigan
United States	Chesapeake Urology Research Associates	Hanover	Maryland
United States	Houston Methodist Hospital - Department of Urology	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	University of California - Irvine Medical Center	Irvine	California
United States	University of Florida	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Tower Urology	Los Angeles	California
United States	Urology Group of Southern California / American Institute of Research	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Clinical Research Solutions - Helios Clinical Research	Middleburg Heights	Ohio
United States	Froedtert Hospital / Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Carolina Urologic Research Center, LLC	Myrtle Beach	South Carolina
United States	Mount Sinai Medical Center	New Haven	New York
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	Associated Urologists of North Carolina	Raleigh	North Carolina
United States	Genesis Research	San Diego	California
United States	Urological Associates of South Arizona	Tucson	Arizona
United States	New Jersey Urology, LLC	Voorhees	New Jersey
United States	The George Washington Medical Faculty Associates	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
enGene, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0.	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
Primary	Phase 2: Percentage of patients with cystoscopic CR at 48 weeks, based on exam, urine cytology and appropriate biopsies.	Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease.	Approximately 48 weeks
Primary	Phase 2: Nature, incidence, relatedness, and severity of treatment emergent adverse events (as assessed by CTCAE v5.0)	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	Phase 1: The number of patients who experience a DLT through the end of Cycle 1	To identify the number of patients who experience a DLT through the end of Cycle 1	Approximately 12 Weeks
Secondary	Phase 1: CR rate to EG-70 by cystoscopy at approximately 12 weeks.	To evaluate preliminary efficacy of EG-70 by 12 weeks via cystoscopy	Approximately 12 weeks
Secondary	Phase 2: Progression-free survival (PFS)	To evaluate disease-free survival rate	Approximately 3 years
Secondary	Phase 2: CR rate at 12, 24, 36, and 96 weeks	To further evaluate CR at the efficacy analysis following each cycle.	Approximately 12, 24, 36, and 96 weeks
Secondary	Phase 2: Duration of response of the responding patients	Durability will be measured by determining the number of patients without recurrence of high-grade disease.	Approximately 3 years
Secondary	Phase 2: Quality of Life Assessment	Health-related quality of life	24 weeks