A Phase 1, Open-label Trial of Belzupacap Sarotalocan (AU-011) in Bladder Cancer

Phase 1

Recruiting

• Conditions: Non-muscle-invasive Bladder Cancer; Non-Muscle Invasive Bladder Cancer (&Amp;#34;NMIBC&Amp;#34;) Unresponsive/Intolerant to BCG; NMIBC; Non-Muscle Invasive Bladder Carcinoma; Non-Muscle Invasive Bladder Neoplasms; Non-Muscle Invasive Bladder Urothelial Carcinoma; Urothelial Carcinoma Bladder
• Interventions: Drug: AU-011; Combination Product: AU-011 in Combination with Medical Laser Adminstration; Combination Product: AU-011 in Combination with Medical Laser Administration

• Registration Number: NCT05483868
• Lead Sponsor: Aura Biosciences

Brief Summary

The main objectives of this study are to determine the feasibility and safety of Belzupacap Sarotalocan (AU-011, bel-sar) treatment of bladder cancer utilizing focal injections with or without laser application.

Detailed Description

Aura is enrolling participants with urothelial carcinoma to evaluate the safety, technical feasibility, and preliminary efficacy of bel-sar. The goal is to achieve the trial objectives with minimal disruption to the standard of care (SoC) of the treating Investigator.

Study Timeline

• Study First Submitted: 2022-07-20
• Study First Submitted QC: 2022-07-29
• Study First Posted: 2022-08-02
• Study Start: 2022-09-26
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-29
• Last Update Posted: 2025-10-03
• Primary Completion: 2026-12
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

1. Meet the following histopathologic requirements for urothelial carcinoma:

   • For Cohorts 1b, 4a-c:

   histopathological diagnosis of NMIBC (any grade) is required. For participants with first diagnosis of NMIBC, confirmation of urothelial carcinoma by recent biopsy (≤6 months of Screening Visit) is required. Participants with recurrent NMIBC must have a current lesion that clinically appears to be NMIBC with histopathologic confirmation based on TURBT or biopsy within the last 24 months).

   For Cohorts 4d, 4e, 4g and 4h, a diagnosis of LG IR NMIBC (according to

   AUA risk classification guidelines) is required, specifically:

   • Multifocal LG Ta; OR
   • Solitary LG Ta >3 cm; OR
   • Low-grade Ta with prior recurrence(s) within 1 year.

   For Cohorts 4f and 4i, a diagnosis of HR NMIBC (according to AUA risk classification guidelines) is required, specifically:

   • Ta HG papillary disease with or without CIS; OR

   • T1 papillary disease with or without CIS

   • Participants may be BCG-naïve or may have received prior treatment with BCG for HR or IR NMIBC (BCG-exposed, BCG-failed, BCG-intolerant)

   • BCG-refractory participants are excluded. BCG-refractory is defined by the following:

     • Persistent HG disease at 6 months following adequate BCG (defined as ≥5/6 induction instillations and ≥2 additional doses, either from re-induction or maintenance), OR
     • HG T1 disease at first evaluation (3 months) after BCG, OR
     • Persistent CIS that remains despite a second BCG course, OR
     • Disease progression in stage or grade during BCG therapy, including maintenance

2. Have no evidence of current or prior metastatic urothelial carcinoma

3. Adequate bone marrow, renal, and hepatic function

Exclusion Criteria

1. Any additional malignancy that requires active treatment, unless deemed appropriate after discussion by the Investigator with the trial's Medical Monitor.
2. Used an investigational drug or medical device within 30 days or 5 half-lives (whichever is longer) of Visit 1 or be concurrently enrolled in another investigational trial.
3. Active bacterial, fungal, or viral infections - all prior infections must have resolved following optimal therapy and subject must be off all systemic anti-infective agents.
4. Active autoimmune disease, chronic inflammatory condition, or other conditions (like solid organ transplant or bone marrow allograft) requiring concurrent use of any systemic immunosuppressants or steroids.
5. Chronic active hepatitis B or C and HIV.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Focal injections of AU-011 prior to TURBT (1b)	AU-011	Intratumoral (50 μg) and intramural (50 μg) injection of AU-011 prior to the standard of care (TURBT) in patients with NMIBC.
Focal injections of AU-011 with laser application before TURBT (4a)	AU-011 in Combination with Medical Laser Adminstration	Intratumoral (50 μg) and intramural (50 μg) injection of AU-011 with laser application before standard of care (TURBT) in patients with NMIBC.
Focal injection of AU-011 with laser application before TURBT (4b)	AU-011 in Combination with Medical Laser Administration	Focal injection of AU-011 (100 μg) with laser application before standard of care (TURBT) in patients with NMIBC.
Focal injection of AU-011 with laser application before TURBT (4c)	AU-011 in Combination with Medical Laser Administration	Focal injection of AU-011 (200 μg) with laser application before standard of care (TURBT) in patients with NMIBC.
Focal injection of AU-011 and laser application with option for TURBT (4d)	AU-011 in Combination with Medical Laser Administration	Participants with intermediate-risk NMIBC will receive multiple treatment cycles of focal AU-011 (200 ug per lesion) with laser treatment and option for TURBT in patients with intermediate risk NMIBC. Participants will be evaluated for safety and response to AU-011 up to 12 months from initiation of treatment.
Focal injection of AU-011 and laser application with option for TURBT (4e)	AU-011 in Combination with Medical Laser Administration	Participants with intermediate-risk NMIBC will receive multiple treatment cycles of focal AU-011 (400 µg per lesion) followed by laser activation, with the option for TURBT. Participants will be evaluated for safety and response to AU-011 for up to 12 months from initiation of treatment. Enrollment will occur in parallel with Cohort 4g, with randomized (1:1) assignment.
Focal injection of AU-011 and laser application with mandatory TURBT (4f)	AU-011 in Combination with Medical Laser Administration	Participants with high-risk NMIBC will receive multiple treatment cycles of focal AU-011 (400 µg per lesion) followed by laser activation prior to mandatory TURBT. Participants will be evaluated for safety and response to AU-011 for up to 12 months from initiation of treatment.
Focal injection of AU-011 and laser application with optional TURBT (4g)	AU-011 in Combination with Medical Laser Administration	Participants with intermediate-risk NMIBC will receive multiple treatment cycles of focal AU-011 (400 µg per lesion) followed by laser activation with the option of TURBT. Participants will be evaluated for safety and response to AU-011 for up to 12 months from initiation of treatment. Enrollment will occur in parallel with Cohort 4e, with randomized (1:1) assignment.
Focal injection of AU-011 and laser application with option for TURBT (4h)	AU-011 in Combination with Medical Laser Administration	Participants with intermediate-risk NMIBC will receive multiple treatment cycles of focal AU-011 (800 ug per lesion) with laser treatment and option for TURBT. Participants will be evaluated for safety and response to AU-011 up to 12 months from initiation of treatment. This arm is optional and will be run at the discretion of the sponsor.
Focal injection of AU-011 and laser application with mandatory TURBT (4i)	AU-011 in Combination with Medical Laser Administration	Participants with high-risk NMIBC will receive multiple treatment cycles of focal AU-011 (800 µg per lesion) before mandatory TURBT. Participants will be evaluated for safety and response to AU-011 up to 12 months from initiation of treatment. This arm is optional and will be run at the discretion of the sponsor.

Primary Outcome Measures

Name	Time	Method
Safety of AU-011: Incidences of SAEs and DLTs	up to 12 months	Incidence and severity of treatment-related adverse events \[time frame 12 months\], serious adverse events \[time frame 12 months\], and incidence of dose-limiting toxicities \[time frame 14 days\]

Secondary Outcome Measures

Name	Time	Method
Complete response (CR) rate	at the 3-month time point and at TURBT	for all cohorts
Duration of response (DoR)	12 months	In participants who achieve CR
Durable CR rate	6-, 9-, and 12-month follow-up	Proportion of participants maintaining a CR after achieving a CR
Recurrence-free survival (RFS)	12 mos	Participants in neoadjuvant cohorts

Trial Locations

Locations (10)

Urology Clinics of North Texas; 🇺🇸 Dallas, Texas, United States

The Urology Place; 🇺🇸 San Antonio, Texas, United States

Arkansas Urology; 🇺🇸 Little Rock, Arkansas, United States

Saint John's Cancer Institute; 🇺🇸 Santa Monica, California, United States

Montefiore Medical Center; 🇺🇸 The Bronx, New York, United States

Carolina Urologic Research Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Urology Associates, P.C.; 🇺🇸 Nashville, Tennessee, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

The University of Texas San Antonio; 🇺🇸 San Antonio, Texas, United States

Urology San Antonio/USA Clinical Trials; 🇺🇸 San Antonio, Texas, United States