A Study of STM-416 Administered to Patients Undergoing TURBT for Recurrent Bladder Cancer

Study Overview
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Brief Summary
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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
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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 4 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 24 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.

Official Title
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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

Conditions
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Non-muscle-invasive Bladder Cancer

Intervention / Treatment
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* Drug: STM-416


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are aged 18 years or older; 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; Are considered high risk for recurrence; Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2; 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: Have a history of CIS or MIBC; Are receiving any other investigational agents; 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; 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; 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Singe group assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STM-416<br>STM-416 | Drug: STM-416<br>* STM-416 monotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities (DLTs) [Safety and Tolerability] Phase 1 | Incidence of dose-limiting toxicities (DLTs) over the first 21-days of study treatment | 21 days | 
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Phase 1 | Incidence of serious adverse events (SAEs), and adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 | Time on trial up to 90 days | 
| Recurrence free survival time (Phase 2a) | Recurrence will be evaluated by cystoscopy and urine cytology | Through study completion up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of STM-416 (Phase 1) | Maximum plasma concentration (Cmax) of resiquimod (R848) in patient blood for the single dose level (Phase 1) | Day 0, post 24 hours, post 24 hour | 
| Pharmacokinetics of STM-416 (Phase 1) | Area under the plasma concentration versus time curve (AUC) of resiquimod (R848) in patient blood for the single dose level (Phase 1) | Day 0, post 24 hours, post 24 hour | 
| Pharmacodynamics of STM-416 | Pharmacodynamic assessments in plasma and urine will be listed and summarized by dose level for Phase 1/2a | Day 0, post 24 hours, post 48 hours, post 21 days, post 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCG, Open-label, Dose escalation, STM-416, Resiquimod, Toll-like receptor 7/8, Non-Muscle Invasive Bladder Cancer, TURBT, Immunotherapy