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BRIEF TITLE: INtravesical STING Agonist E7766 in NMIBC Including Subjects Unresponsive to BCG Therapy, INPUT-102

INtravesical Phase 1/1b Study of STING Agonist E7766 in NMIBC Including Subjects Unresponsive to BCG Therapy, INPUT-102


  • Org Study ID: E7766-G000-102
  • Secondary ID: 2019-000161-21
  • NCT ID: NCT04109092
  • NCT Alias:
  • Sponsor: Eisai Inc. - Industry
  • Source: Eisai Inc.

Brief Summary

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.

Overal Status Start Date Phase Study Type
Recruiting February 13, 2020 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)

Primary Outcome 1 - Time Frame: Baseline up to 6 weeks of the Induction Cycle (Cycle length is equal to [=] 6 weeks)

Primary Outcome 2 - Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Primary Outcome 2 - Time Frame: Baseline up to 30 days after the last dose of study drug (approximately 42 months)

Primary Outcome 3 - Measure: Dose Expansion Part: Complete Response Rate (CRR) at 3 Months

Primary Outcome 3 - Time Frame: Up to 3 months

Primary Outcome 4 - Measure: Dose Expansion Part: CRR at 6 Months

Primary Outcome 4 - Time Frame: Up to 6 months

Primary Outcome 5 - Measure: Dose Expansion Part: CRR at 12 Months

Primary Outcome 5 - Time Frame: Up to 12 months

Primary Outcome 6 - Measure: Dose Expansion Part: CRR at 18 Months

Primary Outcome 6 - Time Frame: Up to 18 months

Primary Outcome 7 - Measure: Dose Expansion Part: CRR at 24 Months

Primary Outcome 7 - Time Frame: Up to 24 months

Condition:

  • Urinary Bladder Neoplasms

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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Eisai Medical Information

Phone: 1-888-274-2378

Email: esi_oncmedinfo@eisai.com

Locations

Facility Status Contact
Banner MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Recruiting
University of Southern California
Los Angeles, California 90033
United States
Not yet recruiting
UCLA
Santa Monica, California 90404
United States
Recruiting
Mayo Clinic Jacksonville
Jacksonville, Florida 32224
United States
Not yet recruiting
Indiana University
Indianapolis, Indiana 46202
United States
Not yet recruiting
Washington University
Saint Louis, Missouri 63110
United States
Not yet recruiting
The Mount Sinai Hospital
New York, New York 10029
United States
Recruiting
Cleveland Clinic
Cleveland, Ohio 44195
United States
Not yet recruiting
Ohio State University
Columbus, Ohio 43210
United States
Not yet recruiting