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

INTRODUCTION

  • Org Study ID: EG-70-101
  • Secondary ID: N/A
  • NCT ID: NCT04752722
  • Sponsor: enGene, Inc.

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.

  • Overall Status
    Recruiting
  • Start Date
    April 22, 2021
  • Phase
    PHASE1, PHASE2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

  • Superficial Bladder Cancer
  • Non-muscle Invasive Bladder Cancer With Carcinoma in Situ

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 effective double-barrier contraception and for 3 months 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 (LAR) 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. Consideration by the Investigator that the patient is an unsuitable candidate for the study.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Christine Tosone, Ms, RAC

Role: Study Director

Affiliation: enGene, Inc.

Overall Contact

Name: Chris Tosone

Phone: 5143324888

Email: clinicaltrials@engene.com

LOCATION

Facility Status Contact
Facility: Urological Associates of South Arizona
Tucson, Arizona 85715
United States
Status: Recruiting Contact: Contact
Susan Kalota
520-795-5830
skalota1@gmail.com

Facility: Urology Group of Southern California / American Institute of Research
Los Angeles, California 90017
United States
Status: Recruiting Contact: Contact
Joél Barra
213-481-7142
jbarra@airesearch.us

Facility: USC/Norris Comprehensive Cancer Center
Los Angeles, California 90033
United States
Status: Recruiting Contact: Contact
Anne Schuckman
323-865-3700
anne.schuckman@med.usc.edu

Facility: Tower Urology
Los Angeles, California 90048
United States
Status: Recruiting Contact: Contact
Terry Williams
310-854-9898
178
williamst@towerurology.com

Facility: Genesis Research
San Diego, California 92123
United States
Status: Recruiting Contact: Contact
Alanna Gavriushina
858-430-1101
2670
Alanna.gavriushina@uniohp.com

Contact
Katayune Golshan
Katayune.golshan@uniohp.com

Facility: The George Washington Medical Faculty Associates
Washington, District of Columbia 20037
United States
Status: Recruiting Contact: Contact
Michael Whalen
202-741-2798
mwhalen@mfa.gwu.edu

Facility: University of Florida
Jacksonville, Florida 32209
United States
Status: Recruiting Contact: Contact
Kethandapatti Balaji
904-244-7340
kc.balaji@jax.ufl.edu

Facility: Emory University
Atlanta, Georgia 30322
United States
Status: Recruiting Contact: Contact
Shreyas Joshi
404-778-4898
shreyas.joshi@emory.edu

Facility: University of Kansas Medical Center
Kansas City, Kansas 66160
United States
Status: Recruiting Contact: Contact
Faith Rahman
913-588-2502
frahman2@kumc.edu

Contact
Laura Mitchell
913-574-2854
Lmitchell11@kumc.edu

Facility: Chesapeake Urology Research Associates
Hanover, Maryland 21076
United States
Status: Recruiting Contact: Contact
Rian Dickstein
rdickstein@cua.md

Facility: Henry Ford Health System
Detroit, Michigan 48202
United States
Status: Recruiting Contact: Contact
Johar Raza, MD
716-697-0305
jraza1@hfhs.org

Facility: Cornwell Health Medical Group and Spectrum Health Hospitals
Grand Rapids, Michigan 49503
United States
Status: Recruiting Contact: Contact
Conrad Tobert
616-267-7333
conrad.tobert3@spectrumhealth.org

Facility: University of Minnesota
Minneapolis, Minnesota 55455
United States
Status: Recruiting Contact: Contact
Marissa Twedt
612-626-6661
twedt050@umn.edu

Contact
Joseph Zabell
zabe0034@umn.edu

Facility: New Jersey Urology, LLC
Voorhees, New Jersey 08043
United States
Status: Recruiting Contact: Contact
Gordon Brown
gbrown@njurology.com

Facility: UNC Chapel Hill Hospital
Chapel Hill, North Carolina 27514
United States
Status: Recruiting Contact: Contact
Marc Bjurlin
919-966-8217
marc_bjurlin@med.unc.edu

Facility: Associated Urologists of North Carolina
Raleigh, North Carolina 27612
United States
Status: Recruiting Contact: Contact
Mark Jalkut
919-782-1255
mjalkut@gmail.com

Facility: University of Cincinnati Medical Center
Cincinnati, Ohio 45219
United States
Status: Recruiting Contact: Contact
Mohammed Kamel
513-558-0983
kamelme@ucmail.uc.edu

Facility: Clinical Research Solutions - Helios Clinical Research
Middleburg Heights, Ohio 44130
United States
Status: Recruiting Contact: Contact
Kara Lasorella
440-340-9010
kara.lasorella@heliosclinical.com

Facility: Oregon Health & Science University (OHSU)
Portland, Oregon 97239
United States
Status: Recruiting Contact: Contact
J Liu
610-659-7113
jenj@ohsu.edu

Facility: Carolina Urologic Research Center, LLC
Myrtle Beach, South Carolina 29572
United States
Status: Recruiting Contact: Contact
Neal Shore
843-449-1010
nshore@auclinics.com

Facility: UT Southwestern Medical Center
Dallas, Texas 75390
United States
Status: Recruiting Contact: Contact
Jose Santoyo
214-645-8764
jose.santoyo@utsouthwestern.edu

Contact
Yair Lotan
Yair.Lotan@UTSouthwestern.edu

Facility: Houston Methodist Hospital - Department of Urology
Houston, Texas 77030
United States
Status: Recruiting Contact: Contact
Taliah Muhammad
346-238-4523
tnmuhammad@houstonmethodist.org

Facility: University of Texas - MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: Contact
Ashish Kamat, MD
713-792-3250
akamat@mdanderson.org

Facility: Froedtert Hospital / Medical College of Wisconsin
Milwaukee, Wisconsin 52336
United States
Status: Recruiting Contact: Contact
Scott Johnson
414-955-0867
scjohnson@mcw.edu