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

减法免疫去除术治疗激素折射晚期乳腺癌的评价

• 批准号: 10483880
• 负责人: Christian Shenouda
• 金额: $ 107.23万
• 依托单位: IMMUNICOM, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-08 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10483880
• 关键词: Address; Advanced Malignant Neoplasm; Adverse effects; Adverse event; Aftercare; Antimitotic Agents; Antitumor Response; Apoptosis; Applications Grants; Blood; Blood Component Removal; Breast Cancer Patient; Cancer Etiology; Cancer Patient; Canis familiaris; Cause of Death; Certification; Cessation of life; Chemotherapy-Oncologic Procedure; Clinical; Clinical Data; Clinical Research; Clinical Trials; Comprehensive Cancer Center; Data; Devices; Dose; ERBB2 gene; Eastern Cooperative Oncology Group; Effectiveness; Enrollment; Estrogen receptor positive; European Organization for Research and Treatment of Cancer; Evaluation; Event; Excision; Flow Cytometry; Goals; Hand; Health Status; Hormones; Image; Immune; Immune response; Immune system; Immunohistochemistry; Immunotherapy; Incidence; Investigation; Israel; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Mediating; Medical; Medical Device; Medicine; Meleagris gallopavo; Metastatic breast cancer; Monitor; Neoplasm Circulating Cells; Nivolumab; Non-Small-Cell Lung Carcinoma; Oncology; Outcome; Patient-Focused Outcomes; Patients; Performance; Phase; Physician Executives; Plasma; Poland; Population; Procedures; Process; Prognosis; Progression-Free Survivals; Protocols documentation; Quality of life; Refractory; Resistance; Safety; Sampling; Secure; Small Business Innovation Research Grant; Solid; Solid Neoplasm; System; T-Lymphocyte; TNF gene; TNFRSF1A gene; Technology; Testing; Therapeutic; Tissues; Tumor Burden; Tumor Markers; Validation; Walking; Whole Blood; Woman; Work; advanced breast cancer; advanced disease; arm; base; blood filtration; chemotherapy; clinical efficacy; cohort; college; commercialization; comparative; cytokine; design; efficacy study; follow-up; grasp; hormone therapy; immunoregulation; improved; instrument; malignant breast neoplasm; melanoma; neoplastic cell; novel; pre-clinical; primary outcome; programmed cell death ligand 1; programmed cell death protein 1; programs; recruit; research clinical testing; response; response biomarker; secondary outcome; success; treatment response; triple-negative invasive breast carcinoma; tumor; tumor necrosis factor-alpha inhibitor

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.

摘要： Immunicom将其临床工作重点放在验证一种首创的突破性免疫治疗设备上， 治疗多种实体瘤癌症。该装置，一个消减免疫分离柱，具体地说， 减少循环可溶性TNF-α受体（sTNF-Rs），其抑制TNF-α的肿瘤杀伤作用， 免疫调节活性。这种治疗方法旨在增强患者自身的先天性体液免疫， 免疫反应Immunicom的目标是证明这种免疫疗法的选择， 难治性/晚期癌症，在无进展生存期方面提供更有效的结局， 在治疗期间维持生活质量指标。Immunicom的临床项目是开发其 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 先进的治疗方案 Immunicom正在贝勒医学院提议对LW-02免疫单采设备进行试验，用于治疗 难治性转移性激素抵抗性乳腺癌ER+/Her 2-乳腺癌治疗失败的患者 激素治疗和化疗通常都没有继续治疗的选择， 大多数患者的5年预后差得不可接受。 Immunicom提议在12名受试者中进行一项探索性研究，主要评估其安全性和耐受性。 免疫治疗LW-02设备在这个乳腺癌人群。疗效将集中于从 病人的血液循环。至少两种激素治疗失败的乳腺癌患者，以及 将招募一到二线化疗患者接受LW-02装置的单药治疗， 周的时间，然后联合艾日布林化疗，另外12周。在整个治疗过程中， 将监测患者循环sTNF-R的减少和不良事件。客观缓解/临床 获益将是探索性的;生活质量/临床功能、循环肿瘤细胞和免疫学标志物 也将评估反应（包括组织中）。将监测对治疗/肿瘤负荷的临床应答 根据RECIST v1.1/iRECIST标准（MRI/CT）。长达1年的随访将包括评价受试者的 无进展生存期（PFS）、最佳总体缓解（BOR）、总体缓解率（ORR）和总体生存期。 这项探索性研究将提供难治性ER+/HER 2-乳腺癌的关键安全性和有效性数据， Immunicom在这一特定患者队列中进行更大规模的疗效研究，并扩大令人鼓舞的 来自正在进行的TNBC、NSCLC、黑色素瘤研究的大量安全性、耐受性和有效性数据 和其他实体瘤。这项试验将证明免疫单采术是否可以作为一种治疗选择， 难治性、激素抵抗性乳腺癌，单独使用或与化疗方案联合使用。患乳腺癌后， 作为女性第二大常见癌症和主要死亡原因，需要额外的治疗选择 为晚期疾病患者提供更好的治疗结果。