A Phase 1, Open-label Trial of Belzupacap Sarotalocan (AU-011) to Determine the Feasibility and Safety of Intratumoral Injection With or Without Intramural Injection in Subjects With Bladder Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 55
- 试验地点
- 41
- 主要终点
- Safety of AU-011: Incidences of SAEs and DLTs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Have no evidence of current or prior metastatic urothelial carcinoma
- •Adequate bone marrow, renal, and hepatic function
排除标准
- •Any additional malignancy that requires active treatment, unless deemed appropriate after discussion by the Investigator with the trial's Medical Monitor.
- •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.
- •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.
- •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.
- •Chronic active hepatitis B or C and HIV.
研究组 & 干预措施
Focal injection of AU-011 and laser application with option for TURBT (4h)
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.
干预措施: AU-011 in Combination with Medical Laser Administration (Combination Product)
Focal injections of AU-011 with laser application before TURBT (4a)
Intratumoral (50 μg) and intramural (50 μg) injection of AU-011 with laser application before standard of care (TURBT) in patients with NMIBC.
干预措施: AU-011 in Combination with Medical Laser Adminstration (Combination Product)
Focal injection of AU-011 with laser application before TURBT (4b)
Focal injection of AU-011 (100 μg) with laser application before standard of care (TURBT) in patients with NMIBC.
干预措施: AU-011 in Combination with Medical Laser Administration (Combination Product)
Focal injection of AU-011 with laser application before TURBT (4c)
Focal injection of AU-011 (200 μg) with laser application before standard of care (TURBT) in patients with NMIBC.
干预措施: AU-011 in Combination with Medical Laser Administration (Combination Product)
Focal injection of AU-011 and laser application with mandatory TURBT (4f)
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.
干预措施: AU-011 in Combination with Medical Laser Administration (Combination Product)
Focal injection of AU-011 and laser application with option for TURBT (4e)
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.
干预措施: AU-011 in Combination with Medical Laser Administration (Combination Product)
Focal injection of AU-011 and laser application with option for TURBT (4d)
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.
干预措施: AU-011 in Combination with Medical Laser Administration (Combination Product)
Focal injection of AU-011 and laser application with optional TURBT (4g)
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.
干预措施: AU-011 in Combination with Medical Laser Administration (Combination Product)
Focal injection of AU-011 and laser application with mandatory TURBT (4i)
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.
干预措施: AU-011 in Combination with Medical Laser Administration (Combination Product)
Focal injections of AU-011 prior to TURBT (1b)
Intratumoral (50 μg) and intramural (50 μg) injection of AU-011 prior to the standard of care (TURBT) in patients with NMIBC.
干预措施: AU-011 (Drug)
结局指标
主要结局
Safety of AU-011: Incidences of SAEs and DLTs
时间窗: 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 \[time frame 14 days\]
次要结局
- Complete response (CR) rate(at the 3-month time point and at TURBT)
- Duration of response (DoR)(12 months)
- Durable CR rate(6-, 9-, and 12-month follow-up)
- Recurrence-free survival (RFS)(12 mos)