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

CureBiotech，Inc.，FOA#PA-21-262申请号1121483 项目总结 头颈部鳞状细胞癌(HNSCC)是与癌症相关的第七大原因 世界上最大的死亡率。放射治疗(RT)是局部晚期癌症患者的常规治疗方法。 疾病。手术治疗后局部晚期HNSCC的历史5年总生存率， 化疗，RT为~50%。这些患者中有许多在初次治疗后复发和/或发生转移。 这些患者的预后仍然很差，中位生存期在6至12个月之间。 用抗PD-1抗体进行免疫治疗的应答率不到20%。因此，有一个紧迫的问题 临床需要为复发和/或转移的HNSCC患者开发替代方法。 CureBiotech Inc.是一家临床前阶段的生物技术公司，专注于Toll样受体7/8激动剂， 雷基莫德。FDA批准的Resiquimod比咪喹莫特更有效，生物利用度更好 免疫调节剂。CureBiotech开发了一种创新的肿瘤内控制释放配方 Resiquimod的CB101，它使用聚合物基质将药物隔离到局部位置，目的是 避免全身不良免疫反应。它的治疗效果优于未配制的 Resiquimod在多种临床前模型中的应用。当地晚期或复发的HNSCC很容易获得 瘤内注射CB101。我们推测，CB101将显著增强癌症对 通过调节肿瘤微环境(TME)进行RT。在目标1中，我们将优化剂量和治疗计划 CB101和RT在HNSCC临床前模型中的表达。由于RT可能会增加肿瘤细胞上PD-L1的表达，因此在 目的探讨CB101/RT联合抗PD-1抗体的治疗效果。我们 预期低剂量放射治疗加CB101可能会产生与单独高剂量放射治疗相同或更好的结果 但毒性降低，使RT耐药肿瘤变得敏感，并增强了RT的异位效应。 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员能力。中生成的数据 该项目将包括CB101/RT在HNSCC患者中的I期临床试验的IND应用，以 食品和药物管理局。

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.