A Phase 1/2 Study of EG-70 as an Intravesical Administration to Patients With BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

INTRODUCTION

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

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.

  • Overall Status
    Recruiting
  • Start Date
    April 22, 2021
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0.

Primary Outcome 1 - Timeframe: Approximately 2 years

Primary Outcome 2 - Measure: Phase 2: Percentage of patients with cystoscopic CR at 48 weeks, based on exam, urine cytology and appropriate biopsies.

Primary Outcome 2 - Timeframe: Approximately 48 weeks

Primary Outcome 3 - Measure: Phase 2: Nature, incidence, relatedness, and severity of treatment emergent adverse events (as assessed by CTCAE v5.0)

Primary Outcome 3 - Timeframe: Approximately 3 years

CONDITION

  • Superficial Bladder Cancer

ELIGIBILITY

Inclusion Criteria:
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:
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).

- T1 high grade disease residual at the first evaluation following induction BCG (at least 5 of 6 doses).

- 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).

- Male or non-pregnant, non-lactating female, 18 years or older.
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:
has had a hysterectomy or bilateral oophorectomy or

- is age ≥ 60 years and is amenorrhoeic or

- 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). - 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. - Performance Status: Eastern Cooperative Oncology Group (ECOG) 0, 1, and 2.
Hematologic inclusion within 2 weeks of start of treatment:
Absolute neutrophil count >1,500/mm3.

- Hemoglobin >9.0 g/dl.

- Platelet count >100,000/mm3.
Hepatic inclusion within 2 weeks of Day 1:
Total bilirubin must be ≤1.5 x the upper limit of normal (ULN).

- 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).

- 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.

- Prothrombin time and partial thromboplastin time within the normal limits at Screening.

- Must have satisfactory bladder function with ability to retain study drug for a minimum of 60 minutes.

- Must be willing and able to comply with all protocol requirements.

- Must be willing and able to give informed consent and any authorizations required by local law for participation in the study.
Exclusion Criteria:
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.

- Concurrent treatment with any chemotherapeutic agent.

- Treatment with pembrolizumab within 30 days (Phase 1) or 3 months (Phase 2) prior to Screening.

- 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).

- Women who are pregnant or lactating.

- History of vesicoureteral reflux or an indwelling urinary stent.

- Participation in any other research protocol involving administration of an investigational agent within 1 month prior to Day 1.

- History of radiation to the pelvis.

- History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.

- Evidence of metastatic disease.

- History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.

- History of interstitial cystitis.

- Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.

- Known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.

- Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 5143324888, 5143324888

Email: clinicaltrials@engene.com, clinicaltrials@engene.com

LOCATION

Facility Status Contact
Facility: Urological Associates of South Arizona, PLLC
Tucson, Arizona 85715
United States
Status: Recruiting Contact: N/A
Facility: Urology Group of Southern California
Los Angeles, California 90017
United States
Status: Recruiting Contact: N/A
Facility: University of Minnesota
Minneapolis, Minnesota 55455
United States
Status: Recruiting Contact: N/A
Facility: New Jersey Urology, LLC
Voorhees, New Jersey 08043
United States
Status: Recruiting Contact: N/A
Facility: UT Southwestern Medical Center
Dallas, Texas 75390
United States
Status: Recruiting Contact: N/A