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NCT04109092 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: E7766-G000-1022019-000161-21
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 9

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.

Conditions

Urinary Bladder Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)

  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)

• Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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

  Up to 3 months

• Dose Expansion Part: CRR at 6 Months

  Up to 6 months

• Dose Expansion Part: CRR at 12 Months

  Up to 12 months

• Dose Expansion Part: CRR at 18 Months

  Up to 18 months

• Dose Expansion Part: CRR at 24 Months

  Up to 24 months

Secondary Outcomes (6)

• Dose Escalation Part: CRR at 3, 6, 12, 18 and 24 Months

  At Months 3, 6, 12, 18, and 24

• DOCR

  From the date of first documented CR until the first documentation of confirmed disease recurrence (approximately 42 months)

• Local Recurrence Free Rates

  At Months 6, 12, 18, and 24

• Cmax: Maximum Observed Plasma Concentration for E7766

  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)

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7766

  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)

Study Arms (3)

Dose Escalation: NMIBC And BCG Unresponsive NMIBC

EXPERIMENTAL

Drug: E7766

Dose Expansion: CIS With/Without Ta or T1

EXPERIMENTAL

Drug: E7766

Dose Expansion: High-grade Ta or T1, Without CIS

EXPERIMENTAL

Drug: E7766

Interventions

E7766 DRUG

E7766, solution, intravesically.

Dose Escalation: NMIBC And BCG Unresponsive NMIBC; Dose Expansion: CIS With/Without Ta or T1; Dose Expansion: High-grade Ta or T1, Without CIS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Eisai Inc.: lead
• H3 Biomedicine Inc.: collaborator

Study Sites (9)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

UCLA

Santa Monica, California, 90404, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Carcinoma in Situ

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: September 30, 2019
• Study Start: February 13, 2020
• Primary Completion: September 29, 2022
• Study Completion: September 29, 2022
• Last Updated: December 14, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share

Locations

US (9)