Combination of CB101 and radiation therapy in head and neck squamous cell carcinoma

Curebiotech，Inc.，FOA # PA-21-262申请号1121483 项目摘要 头颈部鳞状细胞癌（HNSCC）是癌症相关的第七大原因。 死亡率在世界上。放射治疗（RT）通常用于局部晚期乳腺癌患者。 疾病局部晚期HNSCC手术治疗后的5年总生存率， 化疗，RT约为50%。这些患者中的许多在初始治疗后复发和/或发展为转移性 这些患者的预后仍然很差，中位生存期为6至12个月。 使用抗PD-1抗体的免疫疗法产生的应答率低于20%。因此，有一个紧迫的 临床需要为复发和/或转移性HNSCC患者开发替代方法。 CureBiotech Inc.是一家临床前阶段生物技术公司，专注于Toll样受体7/8激动剂， 瑞喹莫特瑞喹莫特比咪喹莫特更有效，生物利用度更好， 免疫调节药物。CureBiotech开发了一种创新的肿瘤内控释制剂 瑞喹莫特，CB 101，使用聚合物基质将药物螯合到局部部位，目的是 避免系统性不良免疫反应。它显示出优于未配制的上级治疗功效 瑞喹莫特在多个临床前模型中的应用。局部晚期或复发的HNSCC很容易获得， 肿瘤内注射CB 101。我们假设CB 101将显著增强癌症对以下物质的反应： RT通过调节肿瘤微环境（TME）。在目标1中，我们将优化剂量和治疗方案 CB 101和RT在HNSCC临床前模型中的作用。由于RT可能增加肿瘤细胞上PD-L1的表达， 目的2，我们将研究抗PD-1抗体与CB 101/RT组合的治疗效果。我们 预期较低剂量的RT与CB 101可以产生与单独的较高剂量辐射相同或更好的结果 但毒性降低，使RT抗性肿瘤敏感并增强RT的远位效应。 这些目标的成功完成将对未来临床试验的设计产生直接影响。我们有 迅速而细致地实现这些目标的科学和人才能力。中生成的数据 该项目将被纳入CB 101/RT在HNSCC患者中的I期临床试验的IND申请， FDA。

Curebiotech, Inc., FOA # PA-21-262 Application number 1121483 PROJECT SUMMARY Head and neck squamous cell carcinoma (HNSCC) is the seventh leading cause of cancer-related mortality in the world. Radiation therapy (RT) is routinely used for patients with locoregionally advanced disease. The historical 5-year overall survival rates for locally advanced HNSCC after treatment with surgery, chemotherapy, and RT is ~50%. Many of these patients relapse after initial therapy and/or develop metastatic disease, and the prognosis for these patients remains poor, with a median survival between 6 to 12 months. Immunotherapy with anti-PD-1 antibodies yields a response rate less than 20%. Hence, there is a pressing clinical need to develop alternative approaches for patients with relapsed and/or metastatic HNSCC. CureBiotech Inc. is a preclinical stage biotech company that focuses on toll-like receptor 7/8 agonist, resiquimod. Resiquimod is more potent and has better bioavailability than imiquimod, an FDA approved immune modulating drug. CureBiotech has developed an innovative intratumoral controlled release formulation of resiquimod, CB101, which sequesters the drug to a local site using a polymer matrix, with the aim of avoiding systemic adverse immune response. It showed superior treatment efficacy over unformulated resiquimod in multiple preclinical models. Locally advanced or relapsed HNSCC is easily accessible for intratumoral injection of CB101. We postulate that CB101 will significantly augment the response of cancers to RT via modulating the tumor microenvironment (TME). In Aim 1, we will optimize dose and treatment schedule of CB101 and RT in HNSCC pre-clinical models. Since RT may increase PD-L1 expression on tumor cells, in Aim 2, we will investigate the treatment efficacy of anti-PD-1 antibodies with CB101/RT combination. We expect that lower doses of RT with CB101 may yield the same or better results as higher dose radiation alone but with reduced toxicity, making RT resistant tumors sensitive and enhancing the abscopal effect of RT. Successful completion of these aims will have a direct impact on the design of future clinical trials. We have the scientific and personnel capability to achieve these aims quickly and meticulously. The data generated in this project will be included in an IND application of a phase I clinical trial of CB101/RT in HNSCC patients to the FDA.