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
INtravesical Phase 1/1b Study of STING Agonist E7766 in NMIBC Including Subjects Unresponsive to BCG Therapy, INPUT-102
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
Arizona
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Gilbert, Arizona, United States, 85234
- Banner MD Anderson Cancer Center
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California
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Los Angeles, California, United States, 90033
- University of Southern California
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Santa Monica, California, United States, 90404
- UCLA
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic Jacksonville
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University
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New York
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New York, New York, United States, 10029
- The Mount Sinai Hospital
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic
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Columbus, Ohio, United States, 43210
- Ohio State University
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-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Life expectancy greater than (>) 2 years in the view of the investigator.
- Participants must have biopsy proven transitional or predominantly transitional cell NMIBC.
For the Dose Escalation part of the study, the following participants will be included:
Both, lower and higher dose escalation cohorts:
Participants with intermediate risk NMIBC
- 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
- CIS (with or without concomitant non-muscle invasive, Ta or T1 papillary disease) (Arm 1) Or
- 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: is defined as any participant with a high-grade Ta less than or equal to (<=) 3 cm or low-grade T1 tumor or with histologically confirmed multiple and/or recurrent low-grade Ta tumor with either 1 or 2 of the following 4 factors
- Multiple tumors
- Tumor >3 centimeter (cm)
- Early recurrence (less than [<] year)
- Frequent recurrences (>1 per year)
BCG Unresponsive NMIBC is defined as being at least 1 of the following:
- 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.
- Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy.
- 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:
- At least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses of maintenance therapy.
- At least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses of a second induction course.
- 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)
- Participants must consent to repeat blood draws as indicated in the schedule of assessments.
- Participant must consent to providing cystectomy tumor sample in the event that cystectomy is performed following treatment with E7766.
- 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.
- Participants with prior Hepatitis B or C are eligible if they have adequate liver function.
- Left ventricular ejection fraction (LVEF) >50 percent (%) on echocardiography or multiple gate acquisition (MUGA) scan.
- Adequate renal function, bone marrow function and liver function.
Exclusion Criteria:
- 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.
- Participants with any active autoimmune disease or a documented history of autoimmune disease, except for participants with vitiligo or resolved childhood asthma/atopy
- Presence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra or any other regional/metastatic disease.
- Known human immunodeficiency virus (HIV) infection.
- Active infection requiring therapy
- Major surgery within 4 weeks before the first dose of study drug.
- 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).
- Prolongation of corrected QT (corrected for QTc interval using Frederica's correction factors [QTcF]) interval to >480 millisecond (msec) when electrolytes balance is normal.
- Significant cardiovascular impairment.
- Use of illegal recreational drugs.
- 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.
- Currently enrolled in another clinical study or used any investigational drug or device within 28 days preceding Cycle 1 Day 1 (first dosing day).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: Dose Escalation: NMIBC And BCG Unresponsive NMIBC
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E7766, solution, intravesically.
|
|
Experimental: Dose Expansion: CIS With/Without Ta or T1
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E7766, solution, intravesically.
|
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Experimental: Dose Expansion: High-grade Ta or T1, Without CIS
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E7766, solution, intravesically.
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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)
|
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).
|
Baseline up to 6 weeks of the Induction Cycle (Cycle length is equal to [=] 6 weeks)
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|
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to 30 days after the last dose of study drug (approximately 42 months)
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Baseline up to 30 days after the last dose of study drug (approximately 42 months)
|
|
|
Dose Expansion Part: Complete Response Rate (CRR) at 3 Months
Time Frame: Up to 3 months
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Up to 3 months
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|
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Dose Expansion Part: CRR at 6 Months
Time Frame: Up to 6 months
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Up to 6 months
|
|
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Dose Expansion Part: CRR at 12 Months
Time Frame: Up to 12 months
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Up to 12 months
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Dose Expansion Part: CRR at 18 Months
Time Frame: Up to 18 months
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Up to 18 months
|
|
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Dose Expansion Part: CRR at 24 Months
Time Frame: Up to 24 months
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Up to 24 months
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Dose Escalation Part: CRR at 3, 6, 12, 18 and 24 Months
Time Frame: At Months 3, 6, 12, 18, and 24
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At Months 3, 6, 12, 18, and 24
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|
DOCR
Time Frame: From the date of first documented CR until the first documentation of confirmed disease recurrence (approximately 42 months)
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From the date of first documented CR until the first documentation of confirmed disease recurrence (approximately 42 months)
|
|
Local Recurrence Free Rates
Time Frame: At Months 6, 12, 18, and 24
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At Months 6, 12, 18, and 24
|
|
Cmax: Maximum Observed Plasma Concentration for E7766
Time Frame: Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)
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Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)
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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7766
Time Frame: Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)
|
Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)
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|
AUC: Area Under the Plasma Concentration Versus Time Curve for E7766
Time Frame: Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)
|
Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Anticipated)
Primary Completion
Study Completion (Anticipated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- E7766-G000-102
- 2019-000161-21 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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