A Phase I/II Study of EG-70 as an Intravesical Administration to Patients With BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) and High-Risk NMIBC Patients Who Are BCG Naïve or Received Incomplete BCG Treatment

Study Identifier:
EG-70-101
CT.gov Identifier:
NCT04752722
EudraCT Identifier:
202451000000
EU Trial (CTIS) Number:
2024-512900-20-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

To evaluate the safety and tolerability of EG-70 and to determine the recommended Phase 2 dose, followed by a Phase 2 portion to evaluate efficacy and safety.

To 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 or high-risk NMIBC patients who are BCG-naïve or have received incomplete BCG treatment.

To establish efficacy of detalimogene in high-risk NMIBC patients with Cis, as well as those with papillary-only NMIBC.

To evaluate detalimogene in BCG-unresponsive NMIBC patients with Cis.

Response assessed by cystoscopy, urine cytology, biopsy

• If CR or SD at end of Cycle 1, continue with Cycle 2

• After Cycle 2, only patients with a CR will continue for up to 2 more cycles, discontinuation will occur at SD or PD

To evaluate efficacy of EG-70 (determined by Complete Response (CR)) at 48 weeks in each cohort separately and to evaluate the safety of the RP2D of EG-70 administered by intravesical instillation in patients with BCG-unresponsive NMIBC and patients with high-risk NMIBC who are BCG-naïve or have received incomplete BCG treatment.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bladder
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Phase 1
    • Read More
  • Drug: Experimental: Phase 2
  • Drug: Cohorts 2A, 2B and 3: RP2D with eligible high-risk NMIBC patients with CIS who are BCG-naive, BCG-exposed (incompletely treated with BCG) or BCG-unresponsive HG Ta/T1 papillary disease without CIS
  • Drug: Drug: EG-7070 (phase 2)
  • Drug: ASCO GU 2023:
  • Drug: Patients will receive EG-70 for up to 48 weeks and will be followed up for 2yrs. Patients receive at least 1 cycle, and as many as 4 cycles, of the study drug. One cycle is 12 week for once a week for the first 2 weeks of each cycle. Patients may include continuing treatment with an additional dosing cycle.
  • Drug: Phase 1: Patients will receive EG-70 Dosing of 2 or 4 doses in 12-week cycle
  • Drug: Patients are treated with EG-70 at the RP2D (800 µg in 50 mL) by intravesical administration on weeks 1, 2, 5, and 6 of a 12-week cycle, for 4 cycles in one of two cohorts: BCG-unresponsive (Cohort 1); BCG-naive or BCG-incompletely treated (Cohort 2). Patients in either cohort who exhibit stable disease (SD) or CR at week 12 will continue treatment until week 24; patients with progressive disease (PD) will discontinue treatment. Patients who experience or maintain CR at week 24 will receive additional cycles every 12 weeks until week 48; patients with SD or PD at week 24 will discontinue treatment. Patients with PD at any time after week 24 will discontinue treatment.
  • Drug: Patients receive 800µg/mL of detalimogene intravesically at weeks one, two, five, and six during a 12-week cycle, for up to four cycles, with assessments at three, six, nine, and 12 months.
  • Drug: ESMO 2024:
  • Drug: ASCO GU 2025:
  • Drug: CTIS:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • BCG-unresponsive Patients:
    • 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:
    • 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:
    • 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).
    • Male or non-pregnant, non-lactating female, 18 years or older.
    • Women of childbearing potential must have a negative pregnancy test at Screening.
    • 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.
    • 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.
    • Performance Status: Eastern Cooperative Oncology Group 0, 1, and 2.
    • Hematologic inclusion: a. Absolute neutrophil count >1,500/mm3. b. Hemoglobin >9.0 g/dL. c. Platelet count >100,000/mm3.
    • 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.
    • Adequate renal function with creatinine clearance >30 mL/min
    • Prothrombin time and partial thromboplastin time ≤1.25 x ULN or within the therapeutic range if on anticoagulation therapy.
    • Must have satisfactory bladder function with ability to retain study drug for a minimum of 60 minutes.
    • Patient or legally authorized representative must be willing and able to comply with all protocol requirements.
    • Must be willing and able to give informed consent.
    Exclusion criteria
    • Active malignancies (i.e., progressing or requiring treatment change in the last 24 months). Exceptions allowed under Sponsor review.
    • Concurrent treatment with any chemotherapeutic agent.
    • History of partial cystectomy.
    • Treatment with last therapeutic agent (including intravesical chemotherapy post-TURBT) within 30 days of Screening (prior to the screening biopsy).
    • Patients who have received systemic immunosuppressive medication including high-dose corticosteroids.
    • History of severe asthma or other respiratory diseases.
    • 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 30 Days prior to screening or any prior treatment of NMIBC with any investigational gene or immunotherapy agent.
    • 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.
    • Active interstitial cystitis on cystoscopy or biopsy.
    • Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
    • Known human immunodeficiency virus, Hepatitis B, or Hepatitis C infection.
    • Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
    • Hypersensitivity to any of the excipients of the study drug.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruiting
    Condition(s) Treated at Site
    Bladder