Evaluation of Subtractive Immunopheresis for Treatment of Hormone-Refractive Advanced Breast Cancer

摘要： 免疫公司正将其临床工作的重点放在验证一种首个同类的、突破性的免疫治疗设备上 治疗范围广泛的实体肿瘤癌症。该装置为减性免疫分离柱，具体地 减少循环中的可溶性肿瘤坏死因子受体(sTNF-α)，抑制肿瘤坏死因子-α的S杀瘤和 免疫调节活性。这种治疗方法旨在增强患者自身的先天体液 免疫反应。免疫公司的目标是证明这种免疫治疗方案适用于患有 难治性/晚期癌症，在无进展生存率方面提供更有效的结果，而 在治疗期间维持生活质量的措施。免疫公司的临床计划是开发其 免疫分离技术，结合癌症患者的最佳治疗实践，使用当今最 先进的治疗方案。 免疫公司建议在贝勒医学院试验LW-02免疫分离设备，用于治疗 难治性、转移性荷尔蒙抵抗乳腺癌。ER+/Her2-失败的乳腺癌患者 激素治疗和化疗通常都没有多少继续治疗的选择，导致 对于这些患者中的大多数来说，5年预后差得令人无法接受。 免疫研究公司提议对12名受试者进行一项探索性研究，初步评估其安全性和耐受性 LW-02免疫治疗仪在这一乳腺癌人群中的应用。疗效将集中在从 病人的血液在循环。至少两次激素治疗失败的乳腺癌患者，以及 将招募一到两组化疗人员接受LW-02设备的单一治疗，超过四次 疗程一周，然后联合埃布林化疗，再持续12周。在治疗过程中， 将监测患者循环中sTNF-R的减少和不良事件。客观反应/临床 好处将是探索性的；生活质量/临床功能，循环中的肿瘤细胞和免疫学标记 也将评估反应(包括组织中的反应)。将监测临床对治疗的反应/肿瘤负担 按RECIST V1.1/iRECIST标准(MRI/CT)。长达一年的跟踪调查将包括评估受试者 无进展生存率(PFS)、总有效率(BOR)、总有效率(ORR)和总生存率。 这项探索性研究将为难治性ER+/HER2-乳腺癌提供关键的安全性和有效性数据。 为了免疫公司在这一特定的患者队列中进行更大规模的疗效研究，并在令人鼓舞的基础上扩展 来自正在进行的TNBC、NSCLC、黑色素瘤研究的安全性、耐受性和有效性数据 和其他实体瘤。这项试验将证明免疫分离术是否可以作为一种治疗选择 难治的、激素抵抗的乳腺癌，单独或与化疗方案一起使用。患有乳腺癌的患者 女性第二常见的癌症和主要的死亡原因，需要更多的治疗选择 为晚期疾病患者提供更好的预后。

Abstract: Immunicom is focusing its clinical efforts on validating a first-of-its-kind, breakthrough immunotherapy device for treating a wide range of solid tumor cancers. The device, a subtractive immunopheresis column, specifically reduces circulating soluble receptors for TNF-α (sTNF-Rs) that inhibit TNF-α’s tumoricidal and immunomodulatory activity . This therapeutic approach is designed to enhance the patient’s own innate humoral immune response. Immunicom’s goal is to demonstrate this immunotherapy option for patients with refractory/late stage cancers, that provides more effective outcomes in terms of progression free survival, while maintaining quality of life measures while on therapy. Immunicom’s clinical program is to develop its immunopheresis technology, in combination with best treatment practices for cancer patients, using today’s most advanced therapy options. Immunicom is proposing a trial of the LW-02 immunopheresis device, at Baylor College of Medicine, for treating refractory, metastatic hormone resistant breast cancer. Patients with ER+/Her2- breast cancers that have failed both hormonal therapy, and chemotherapy, often have few choices for continuing therapy, resulting in an unacceptably poor 5 year outcome for most of these patients. Immunicom is proposing an exploratory study in 12 subjects to primarily evaluate safety and tolerability of its immunotherapy LW-02 device in this breast cancer population. Efficacy will focus on pull down of sTNF-Rs from the patient’s circulating blood. Breast cancer patients that have failed at least two lines of hormone therapy, and one to two lines of chemotherapy will be recruited to receive monotherapy with the LW-02 device, over a four week period, then in combination with eribulin chemotherapy, for an additional 12 weeks. Throughout treatment, patients will be monitored for reduction of circulating sTNF-Rs and adverse events. Objective response/clinical benefit will be exploratory; quality-of-life/clinical function, circulating tumor cells and markers of an immunologic response (including in tissue) will be evaluate too. Clinical response to treatment/tumor burden will be monitored by RECIST v1.1/iRECIST criteria (MRI/CT). Follow-up for up to 1 year will include evaluating subjects for progression free survival (PFS), best overall response (BOR), overall response rate (ORR), and overall survival. This exploratory study will provide critical safety and effectiveness data in refractory ER+/HER2- breast cancer, for Immunicom to pursue a larger efficacy study in this specific cohort of patients and expand on the encouraging body of safety, tolerability and effectiveness data emanating from ongoing studies in TNBC, NSCLC, melanoma and other solid tumor. This trial will demonstrate if immunopheresis could be a therapeutic option for treating refractory, hormone resistant breast cancer, alone or with chemotherapy regimens. With breast cancer the second most common cancer and leading cause of death in women, additional therapeutic options are needed to provide better outcomes for patients with advanced disease.