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

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 (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. 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: enGene clinical trials, Chris Tosone

Phone: +18572991097

Email: clinicaltrials@engene.com

LOCATION