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

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 Patients:
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) after receiving at least one induction course of intravesical BCG (at least 5 of 6 induction doses) or recurrence after 12 months of receiving at least one induction course of intravesical BCG (at least 5 of 6 induction doses), or

- T1 high grade disease residual at the first evaluation following induction BCG (at least 5 of 6 doses).
BCG-Naïve or BCG-incompletely treated Patients (Phase 2 Only):
NMIBC with 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 1 dose, but not the full course, of intravesical BCG, or

- high-grade disease (Ta, T1, or Tis) who have not yet received any treatment with BCG, or

- T1 high grade disease residual at the first evaluation following incomplete treatment with BCG
Patients who have previously been treated with at least one dose of intravesical chemotherapy at TURBT are eligible for inclusion one month post-treatment.
All Patients:
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.

- Patient or legally authorized representative (LAR) must be willing and able to comply with all protocol requirements.

- Patient or LAR 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).

- 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 external beam radiation to the pelvis at any time or prostate brachytherapy within the last 12 months.

- 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