Clinical trial NCT05710848: A Study of STM-416 Administered to Patients Undergoing TURBT for Recurrent Bladder Cancer
Official title: A Phase 1/2a Study of STM-416 Administered Intraoperatively to Patients Undergoing Transurethral Resection of Bladder Tumor (TURBT) for Recurrent High-Grade Papillary Bladder Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-muscle-invasive Bladder Cancer
Keywords: Open-label
Dose escalation
STM-416
Resiquimod
Toll-like receptor 7/8
Non-Muscle Invasive Bladder Cancer
TURBT
Immunotherapy
BCG
Lead sponsor: SURGE Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-02-02
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Singe group assignment
Primary purpose: TREATMENT

Brief summary: This is a first-in-human (FIH), Phase 1/2a, multi center, open-label, single treatment, dose escalation and expansion study designed to determine the safety and tolerability of STM-416 in patients with bladder cancer.

Detailed description: This is a 2-part, multicenter, first-in-human (FIH), Phase 1/2a study in patients with a history of pathologically confirmed high-grade Ta or T1 NMIBC without CIS who have completed SOC previously, with recurrent papillary disease seen on cystoscopy, and who are undergoing TURBT without perioperative intravesical chemotherapy. All patients will receive relevant SOC therapy following TURBT. SOC will be administered in the adjuvant setting.

Phase 1 is an open-label, single-treatment, dose-escalation study to evaluate the safety and tolerability of up to 6 increasing doses of intraoperatively administered STM-416 utilizing a 3+3 convention, with 3 to 6 patients enrolled in each STM-416 dose level, with a minimum of 6 patients enrolled at the highest dose level, for a total of approximately 30 patients.

Phase 2a is a randomized, single-blind, single-treatment, dose-expansion study that will comprise 2 arms: TURBT + STM-416 Dose 1 followed by SOC versus TURBT + STM-416 Dose 2 followed by SOC.

Eligibility criteria: Inclusion Criteria:

1. Are aged 18 years or older;
2. Have a history of pathologically confirmed high-grade Ta or T1 NMIBC without CIS who have completed SOC previously, with recurrent papillary disease seen on cystoscopy, and who are undergoing TURBT without perioperative intravesical chemotherapy;
3. Are considered high risk for recurrence;
4. Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2;
5. Have adequate organ and marrow function as defined below:

   * Hemoglobin 9.0 g/dL;
   * Absolute neutrophil count 1.5 × 109/L (1500 per mm3);
   * Platelet count 75 × 109/L (75,000 per mm3);
   * Serum bilirubin 1.5 × institutional upper limit of normal (ULN);
   * AST (serum glutamic-oxaloacetic transaminase)/ALT (serum glutamic-pyruvic transaminase) 2.5 × institutional ULN; and
   * Creatinine CL 60 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine CL: Males: Creatinine CL (mL/min) = Weight (kg) × (140 - Age)/72 × serum creatinine (mg/dL); or Females: Creatinine CL (mL/min) = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL).

Exclusion Criteria:

1. Have a history of CIS or MIBC;
2. Are receiving any other investigational agents;
3. Have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to resiquimod (R848), or excipients used in STM-416 including poloxamer 407 and sodium hyaluronate;
4. Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

   Urinary tract infections are not exclusionary unless they are NCI-CTCAE Grade 3 or higher;
5. Are a woman of childbearing potential regardless of contraceptive use; Note: Women of childbearing potential are only to be excluded in Phase 1 and Phase 2a to avoid bias due to the low prevalence of NMIBC in this population. However, they will be included in subsequent Phase 2/3 studies.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs) [Safety and Tolerability] Phase 1
timeFrame: 21 days
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Phase 1
timeFrame: Time on trial up to 90 days
measure: Recurrence free survival time (Phase 2a)
timeFrame: Through study completion up to 24 months
Secondary outcomes:
measure: Pharmacokinetics of STM-416 (Phase 1)
timeFrame: Day 0, post 24 hours, post 48 hour
measure: Pharmacokinetics of STM-416 (Phase 1)
timeFrame: Day 0, post 24 hours, post 24 hour
measure: Pharmacodynamics of STM-416
timeFrame: Day 0, post 24 hours, post 48 hours, post 21 days, post 90 days
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Urology Specialists
state: Arizona
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, P.C.
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Seth Lerner, MD
role: PRINCIPAL_INVESTIGATOR
References: