An Open-Labeled, Single Arm Phase 2 Efficacy and Safety Study of REM-001 Photodynamic Therapy (PDT) for Treatment of Cutaneous Metastatic Breast Cancer (CMBC)

摘要 皮肤转移性乳腺癌（CMBC）发生在高达24%的转移性乳腺癌患者中。 全身治疗在这种情况下通常疗效有限，手术和放疗只能提供短暂的缓解 由于涉及的副作用和皮肤损害的程度，它们在CMBC人群中的使用可能受到限制。 病变CMBC可引起感染、出血、恶臭和毁容，并可发展为占据大面积 的身体。Kintara提出了一种称为REM-001疗法的光动力疗法（PDT），其中， 光敏药物被注射到体内，在肿瘤部位聚集，并被一种特殊设计的 激光聚焦在选定的病变上。激活的药物破坏肿瘤，对周围环境的影响最小。 组织. REM-001已被证明对许多情况有效，包括CMBC。然而，此前的审判 使用高于阈值的剂量也报告了高比率的不希望的副作用和更长的愈合时间。在 在以前的试验中，焦痂和溃疡等症状增加了恢复时间，并导致患者离开 但与更好的病变结局无关。该项目将减少处理剂量， 先前确定的阈值水平-在最初的研究中显示了79%的响应率-在努力 以减少副作用，同时仍然治疗病变。Kintara将在15名患有以下疾病的患者中测试减少的剂量 有症状的皮肤病变和稳定的全身性疾病，无法接受手术或放疗 在治疗的时候。这些患者将被给予单剂量的REM-001，然后进行光治疗 并将监测疗效（病变缩小或消失，以及疼痛和瘙痒消退， 改善生活质量）和安全性/耐受性（焦痂和溃疡，以及出血和分泌物 病变、治疗相关的光敏性以及标准临床副作用监测）。患者将 继续现有的标准治疗全身治疗，并将在整个试验期间接受治疗。如果这次审判 成功-治疗的病变缩小或消失，减少治疗剂量- Kintara将继续 CMBC的多中心III期试验，并探索REM-001光动力疗法在其他皮肤疾病中的应用 迹象。

ABSTRACT Cutaneous metastatic breast cancer (CMBC) develops in up to 24% of patients with metastatic breast cancer. Systemic therapy often has limited efficacy in such cases, and surgery and radiotherapy offer only transient relief and their use may be limited in the CMBC population due to the side-effects involved and the extent of cutaneous lesions. CMBC can cause infection, bleeding, malodor and disfigurement and can progress to occupy large areas of the body. Kintara proposes a photodynamic therapy (PDT) known as REM-001 Therapy, wherein a photosensitive drug is injected into the body to collect at tumor sites, and is activated by a specially-designed laser focused on the selected lesions. The activated drug destroys tumors with minimal effects to surrounding tissue. REM-001 has been proven to be effective for many conditions, including CMBC. However, previous trials using a higher-than-threshold dose also reported high rates of unwanted side effects and longer healing time. In previous trials, symptoms such as eschar and ulceration increased recovery time and caused patients to leave studies but was not associated with better lesion outcomes. This project will reduce the treatment dosage to the previously identified threshold level – which demonstrated a 79% response rate in an initial study – in an effort to reduce side effects while still treating lesions. Kintara will test the reduced dose on 15 patients with symptomatic cutaneous lesions and stable systemic disease who are unable to receive surgery or radiotherapy at the time of treatment. These patients will be administered a single dose of REM-001 followed by light treatment and will be monitored for efficacy (lesion shrinking or disappearing, as well as pain and itch subsiding and improved quality of life) and safety/tolerability (eschar and ulceration, and bleeding and discharge from the lesions, treatment related photosensitivity, as well as standard clinical side-effect monitoring). Patients will continue on their existing standard of care systemic therapy and will receive it throughout the trial. If this trial is successful – the treated lesions shrink or disappear with the reduced treatment dose – Kintara will continue to a multi-site Phase III trial for CMBC and explore the use of REM-001 photodynamic therapy in other dermal indications.