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A Study of Stimulator of Interferon Genes (STING) Agonist E7766 in Non-muscle Invasive Bladder Cancer (NMIBC) Including Participants Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy, INPUT-102

NCT04109092

Description:

This is an open label, multicenter, phase 1/1b study to assess safety/tolerability and preliminary clinical activity of E7766 as a single agent administered intravesically in participants with NMIBC. Both intermediate risk and BCG-unresponsive NMIBC participants will be included.

Related Conditions:
  • Bladder Carcinoma
  • Bladder Papillary Urothelial Carcinoma
  • Bladder Urothelial Carcinoma
  • Stage 0is Bladder Urothelial Carcinoma
  • Transitional Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Stimulator of Interferon Genes (STING) Agonist E7766 in Non-muscle Invasive Bladder Cancer (NMIBC) Including Participants Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy, INPUT-102
  • Official Title: INtravesical Phase 1/1b Study of STING Agonist E7766 in NMIBC Including Subjects Unresponsive to BCG Therapy, INPUT-102

Clinical Trial IDs

  • ORG STUDY ID: E7766-G000-102
  • SECONDARY ID: 2019-000161-21
  • NCT ID: NCT04109092

Conditions

  • Urinary Bladder Neoplasms

Interventions

DrugSynonymsArms
E7766Dose Escalation: NMIBC And BCG Unresponsive NMIBC

Purpose

This is an open label, multicenter, phase 1/1b study to assess safety/tolerability and preliminary clinical activity of E7766 as a single agent administered intravesically in participants with NMIBC. Both intermediate risk and BCG-unresponsive NMIBC participants will be included.

Detailed Description

      The Phase 1/1b study consist of two parts: Dose Escalation and Dose Expansion. In the Dose
      Escalation Part, E7766 will be administered intravesically to participants with intermediate
      risk NMIBC or participants with BCG unresponsive NMIBC with increased dose levels to assess
      safety/tolerability profile of E7766 and to determine the maximum tolerated dose (MTD) and/or
      recommended Phase 2 dose (RP2D) of E7766. In the Dose Expansion Part, E7766 at RP2D will be
      administered to participants with NMIBC with or without carcinoma in situ (CIS) to confirm
      safety and assess preliminary clinical activity of E7766 as a single agent. Clinical activity
      will be evaluated by complete response (CR) rates at 3 months, 6 months, 12 months, 18
      months, 24 months, and by duration of complete response (DOCR) in all participants who have
      achieved CR on treatment with E7766.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation: NMIBC And BCG Unresponsive NMIBCExperimental
  • E7766
Dose Expansion: CIS With/Without Ta or T1Experimental
  • E7766
Dose Expansion: High-grade Ta or T1, Without CISExperimental
  • E7766

Eligibility Criteria

        Inclusion Criteria:

          1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

          2. Life expectancy greater than (>) 2 years in the view of the investigator.

          3. Participants must have biopsy proven transitional or predominantly transitional cell
             NMIBC.

          4. For the Dose Escalation part of the study, the following participants will be
             included:

               1. Both, lower and higher dose escalation cohorts:

                  Participants with intermediate risk NMIBC

               2. Only higher dose escalation cohorts:

             Participants with BCG Unresponsive NMIBC despite prior adequate treatment.
             Furthermore, all participants should be indicated for radical cystectomy as the
             standard of care for BCG unresponsive NMIBC. Participants who are undergoing radical
             cystectomy as well as participants who have refused to undergo radical cystectomy will
             be eligible to participate in the Dose Escalation part of the study. For participants
             who are undergoing radical cystectomy, date of surgery should not be delayed more than
             3 months after Day 1 of dosing.

             For the Dose Expansion part of the study, the following participants will be included:

             Participants with histologically confirmed

               1. CIS (with or without concomitant non-muscle invasive, Ta or T1 papillary disease)
                  (Arm 1) Or

               2. Non-muscle invasive high-grade Ta or T1 papillary disease without CIS (Arm 2)
                  that is deemed to be unresponsive to BCG therapy despite prior adequate
                  treatment. Furthermore, participants should be indicated for radical cystectomy
                  as the standard of care for BCG unresponsive NMIBC but have refused to undergo
                  radical cystectomy.

             Intermediate risk NMIBC: Histologically confirmed multiple and/or recurrent low grade
             Ta transitional or predominantly transitional cell carcinoma of bladder with either 1
             or 2 of the following factors:

               1. Multiple tumors

               2. Tumor >3 centimeter (cm)

               3. Early recurrence (less than [<] year)

               4. Frequent recurrences (>1 per year)

             BCG Unresponsive NMIBC is defined as being at least 1 of the following:

               1. Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary
                  disease/tumor invades the subepithelial connective tissue) disease within 12
                  months of completion of adequate BCG therapy.

               2. Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG
                  therapy.

               3. T1 high-grade disease at the first evaluation following an induction BCG course

             Adequate BCG therapy is defined as at least 1 of the following:

               1. At least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses
                  of maintenance therapy.

               2. At least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses
                  of a second induction course.

          5. Participants must consent to repeat biopsies to allow the acquisition of fresh
             formalin-fixed paraffin embedded (FFPE) material (obtained within 8 weeks prior to
             treatment initiation with E7766)

          6. Participants must consent to repeat blood draws as indicated in the schedule of
             assessments.

          7. Participant must consent to providing cystectomy tumor sample in the event that
             cystectomy is performed following treatment with E7766.

          8. Immunosuppressive doses of systemic medications, such as steroids or absorbed topical
             steroids (doses >10 milligram per day (mg/d) prednisone or equivalent) must be safely
             discontinued at least 4 weeks before study drug administration.

          9. Participants with prior Hepatitis B or C are eligible if they have adequate liver
             function.

         10. Left ventricular ejection fraction (LVEF) >50 percent (%) on echocardiography or
             multiple gate acquisition (MUGA) scan.

         11. Adequate renal function, bone marrow function and liver function.

        Exclusion Criteria:

          1. Other malignancy active within the previous 2 years except for basal or squamous cell
             skin cancer, or CIS of the cervix or breast that has completed curative therapy.

          2. Participants with any active autoimmune disease or a documented history of autoimmune
             disease, except for participants with vitiligo or resolved childhood asthma/atopy

          3. Presence of concomitant upper tract urothelial carcinoma or urothelial carcinoma
             within the prostatic urethra or any other regional/metastatic disease.

          4. Known human immunodeficiency virus (HIV) infection.

          5. Active infection requiring therapy

          6. Major surgery within 4 weeks before the first dose of study drug.

          7. Concurrent medical condition requiring the use of immunosuppressive medications or
             immunosuppressive doses of systemic medications, such as steroids or absorbed topical
             steroids (doses >10 mg/d prednisone or equivalent).

          8. Prolongation of corrected QT (Corrected QT Interval [QTc]) interval to >480
             millisecond (msec) when electrolytes balance is normal.

          9. Significant cardiovascular impairment.

         10. Use of illegal recreational drugs.

         11. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
             positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin
             [hCG]) test with a minimum sensitivity of 25 International Units Per Liter (IU/L) or
             equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a
             negative screening pregnancy test was obtained more than 72 hours before the first
             dose of study drug.

         12. Currently enrolled in another clinical study or used any investigational drug or
             device within 28 days preceding informed consent.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame:Baseline up to 6 weeks of the Induction Cycle (Cycle length is equal to [=] 6 weeks)
Safety Issue:
Description:DLTs are any of the toxicities occurring during the 6 weeks of the Induction Cycle and assessed by the investigator as related to study drug. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v.5.0).

Secondary Outcome Measures

Measure:Dose Escalation Part: CRR at 3, 6, 12, 18 and 24 Months
Time Frame:At Months 3, 6, 12, 18, and 24
Safety Issue:
Description:
Measure:DOCR
Time Frame:From the date of first documented CR until the first documentation of confirmed disease recurrence (approximately 42 months)
Safety Issue:
Description:
Measure:Local Recurrence Free Rates
Time Frame:At Months 6, 12, 18, and 24
Safety Issue:
Description:
Measure:Cmax: Maximum Observed Plasma Concentration for E7766
Time Frame:Dose Escalation: Induction Phase: Day 1,15: 0-24 hour; Day 8,22,29,36: 0-2 hour; Maintenance Phase: Cycle 1,2,3: Day 1,15: 0-2 hour; Dose Expansion: Induction Phase: Day 1,15,36: 0-2 hour; Maintenance Phase: Cycle 1,2,3: Day 1: 0-2 hour(Cycle=3 weeks)
Safety Issue:
Description:
Measure:Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7766
Time Frame:Dose Escalation: Induction Phase: Day 1,15: 0-24 hour; Day 8,22,29,36: 0-2 hour; Maintenance Phase: Cycle 1,2,3: Day 1,15: 0-2 hour; Dose Expansion: Induction Phase: Day 1,15,36: 0-2 hour; Maintenance Phase: Cycle 1,2,3: Day 1: 0-2 hour(Cycle=3 weeks)
Safety Issue:
Description:
Measure:AUC: Area Under the Plasma Concentration Versus Time Curve for E7766
Time Frame:Dose Escalation: Induction Phase: Day 1,15: 0-24 hour; Day 8,22,29,36: 0-2 hour; Maintenance Phase: Cycle 1,2,3: Day 1,15: 0-2 hour; Dose Expansion: Induction Phase: Day 1,15,36: 0-2 hour; Maintenance Phase: Cycle 1,2,3: Day 1: 0-2 hour(Cycle=3 weeks)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Inc.

Trial Keywords

  • E7766
  • Non-Muscle Invasive Bladder Cancer
  • Intravesical administration
  • Ta or T1 Papillary Disease
  • Stimulator of Interferon Genes Agonist
  • Carcinoma in situ
  • BCG Unresponsive

Last Updated

May 12, 2020