Primary Outcome Measures:
- Phase 1: Nature, incidence, relatedness, and severity of all AEs and SAEs according to the CTCAE v5.0. [Time Frame: Approximately 2 years]
- The type, incidence, relatedness and severity of treatment emergent adverse events of EG-70 as assessed by NCI-CTCAE V5.0 will be monitored.
- Phase 2: Percentage of patients with cystoscopic CR at 48 weeks, based on exam, urine cytology and appropriate biopsies. [Time Frame: Approximately 48 weeks]
- Complete response rate will be measured by determining the number of patients without recurrence of high-grade disease.
- Phase 2: Nature, incidence, relatedness, and severity of treatment emergent adverse events (as assessed by CTCAE v5.0) [Time Frame: Approximately 3 years]
- The type, incidence, relatedness and severity of treatment emergent adverse events of EG-70 as assessed by NCI-CTCAE V5.0 will be monitored.
Inclusion Criteria:
BCG-unresponsive Patients:
- BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without resected papillary tumors who are ineligible for or have elected not to undergo cystectomy:
- persistent high-grade disease (Ta, T1, or Tis) after receiving intravesical BCG induction (at least 5 of 6 induction doses) plus maintenance (at least 2 of 3 doses) or recurrence of high-grade papillary disease within 6 months or Tis within 12 months of BCG instillation 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 ineligible for or have elected not to undergo cystectomy:
- persistent high-grade disease (Ta, T1, or Tis):
- after incomplete BCG treatment (at least 1 dose) or
- who have not yet received any treatment with BCG, but who have previously been treated with at least 1 dose of intravesical chemotherapy following transurethral resection of bladder tumor (TURBT)
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.
- In Phase 2, for patients with T1 lesions, Screening biopsy must be considered adequate (contain the muscularis layer).
- 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).
- 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.
- Adequate renal function with creatinine clearance >30 mL/min
- 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.
- History of partial cystectomy.
- Treatment with pembrolizumab within 30 days (Phase 1) or 3 months (Phase 2) prior to Screening.
- Treatment with last therapeutic agent (including intravesical chemotherapy post-TURBT) 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).
- Evidence of persistent or ongoing renal failure.
- History of unresolved vesicoureteral reflux or an indwelling urinary stent.
- History of unresolved hydronephrosis due to ureteral obstruction.
- 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).
Sponsor(s)
enGene, Inc.
Principal Investigator(s)
Michael Whalen, MD
Contact Phone Number
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