Brief Title: EG-70 in Patients With BCG-Unresponsive NMIBC (LEGEND STUDY)

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase 1: Nature

Primary Outcome 1 - Timeframe: Approximately 2 years

Primary Outcome 2 - Measure: incidence

Primary Outcome 2 - Timeframe: Approximately 48 weeks

Primary Outcome 3 - Measure: relatedness

Primary Outcome 3 - Timeframe: Approximately 3 years

Primary Outcome 4 - Measure: and severity of all AEs and SAEs according to the CTCAE v5.0.

Primary Outcome 4 - Timeframe: N/A

Primary Outcome 5 - Measure: Phase 2: Percentage of patients with cystoscopic CR at 48 weeks

Primary Outcome 5 - Timeframe: N/A

Primary Outcome 6 - Measure: based on exam

Primary Outcome 6 - Timeframe: N/A

Primary Outcome 7 - Measure: urine cytology and appropriate biopsies.

Primary Outcome 7 - Timeframe: N/A

Primary Outcome 8 - Measure: Phase 2: Nature

Primary Outcome 8 - Timeframe: N/A

Primary Outcome 9 - Measure: incidence

Primary Outcome 9 - Timeframe: N/A

Primary Outcome 10 - Measure: relatedness

Primary Outcome 10 - Timeframe: N/A

Primary Outcome 11 - Measure: and severity of treatment emergent adverse events (as assessed by CTCAE v5.0)

Primary Outcome 11 - 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 CIS disease within 12 months of treatment 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
Phase 2 Only:

- 2. BCG-Naïve or BCG-incompletely treated Patients with CIS or BCG-unresponsive, HG Ta/T1 papillary disease without CIS:
-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: cohort 2a) no treatment with BCG but may 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 cohort 2b) indicated by pathology incomplete BCG treatment (at least 1 dose and less than the 5+2 doses required for adequate dosing per Cohort 1) or cohort 3) patients who are BCG-unresponsive following adequate treatment, with HG Ta/T1 papillary disease without CIS.
All Patients:

- 3. Patients who have previously been treated with a checkpoint inhibitor 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; 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 may be eligible after repeat TURBT if pathology shows non-invasive (Ta or less) or no disease.

- 8. Performance Status: Eastern Cooperative Oncology Group 0, 1, and 2.

- 9. Hematologic inclusion: a. Absolute neutrophil count >1,500/mm3. b. Hemoglobin >9.0 g/dL. c. Platelet count >100,000/mm3.

- 10. Hepatic inclusion: a. Total bilirubin must be ≤1.5 x the upper limit of normal (ULN). b. 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 60 minutes.
Exclusion Criteria:
1. Active malignancies (i.e., progressing or requiring treatment change in the last 24 months). Exceptions allowed under Sponsor review.

- 2. Concurrent treatment with any chemotherapeutic agent.

- 3. History of partial cystectomy.

- 4. Treatment with last therapeutic agent (including intravesical chemotherapy post-TURBT) within 30 days of Screening (prior to the screening biopsy).

- 5. Patients who have received systemic immunosuppressive medication including high-dose corticosteroids.

- 6. History of severe asthma or other respiratory diseases.

- 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 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.

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: enGene clinical trials, Chris Tosone

Phone: +18572991097

Email: [email protected]

LOCATION