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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

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

INTRODUCTION

  • Org Study ID: E7766-G000-102
  • Secondary ID: 2019-000161-21
  • NTC ID: NCT04109092
  • Sponsor: 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.


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

PRIMARY OUTCOMES

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

Primary Outcome 1 - Timeframe: 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 - Timeframe: 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 - Timeframe: Up to 3 months

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

Primary Outcome 4 - Timeframe: Up to 6 months

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

Primary Outcome 5 - Timeframe: Up to 12 months

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

Primary Outcome 6 - Timeframe: Up to 18 months

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

Primary Outcome 7 - Timeframe: Up to 24 months

CONDITION

  • Urinary Bladder Neoplasms

ELIGIBILITY


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: 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

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 for QTc interval using Frederica's correction
factors [QTcF]) 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 Cycle 1 Day 1 (first dosing day).

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 1-888-274-2378

Email: esi_oncmedinfo@eisai.com

LOCATION

Facility Status Contact
Facility: Banner MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Status: Recruiting Contact: N/A
Facility: UCLA
Santa Monica, California 90404
United States
Status: Recruiting Contact: N/A
Facility: The Mount Sinai Hospital
New York, New York 10029
United States
Status: Recruiting Contact: N/A