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

CB101与放射治疗联合治疗头颈部鳞状细胞癌

• 批准号: 10545347
• 负责人: Amit Maity
• 金额: $ 25.09万
• 依托单位: CUREBIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545347
• 关键词: Abscopal effect; Adverse effects; Aftercare; Agonist; Antigen Presentation; Antigen-Presenting Cells; Antigens; Antitumor Response; Biological Availability; Biotechnology; CD8-Positive T-Lymphocytes; CD8B1 gene; Cancer Etiology; Cancer Patient; Cancer Vaccines; Chemotherapy and/or radiation; Clinical; Clinical Trials; Combined Modality Therapy; Cutaneous T-cell lymphoma; Cytotoxic T-Lymphocytes; Data; Dendritic Cells; Disease; Distant; Dose; Drug Targeting; Exhibits; FDA approved; Formulation; Fractionation; Future; Generations; Goals; Growth; Head and Neck Squamous Cell Carcinoma; Human Resources; Imiquimod; Immune; Immune response; Immunity; Immunologic Adjuvants; Immunomodulators; Immunotherapy; Injections; Low Dose Radiation; MHC Class I Genes; Malignant Neoplasms; Modeling; Mus; Operative Surgical Procedures; Patients; Pharmaceutical Preparations; Phase I Clinical Trials; Polymers; Pre-Clinical Model; Process; Production; Prognosis; Publishing; Radiation; Radiation Dose Unit; Radiation Oncology; Radiation therapy; Relapse; Site; Skin Cancer; Survival Rate; T-Lymphocyte; TLR7 gene; Testing; Therapeutic; Time; Topical agent; Toxic effect; Treatment Efficacy; Treatment Protocols; Tumor Antigens; Tumor-infiltrating immune cells; Work; advanced disease; anti-PD1 antibodies; anti-PD1 therapy; anti-tumor immune response; antitumor effect; base; cancer cell; cancer therapy; controlled release; curative treatments; cytokine; cytotoxic CD8 T cells; design; disease prognosis; early phase clinical trial; experience; immune checkpoint blockade; immunogenic cell death; immunoreaction; innovation; mortality; neoplastic cell; novel strategies; optimal treatments; patient prognosis; pre-clinical; programmed cell death ligand 1; programmed cell death protein 1; relapse patients; resiquimod; response; therapy resistant; tumor; tumor growth; tumor microenvironment

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.

Curebiotech, Inc.，FOA # PA-21-262 申请号 1121483 项目概要 头颈鳞状细胞癌 (HNSCC) 是癌症相关的第七大原因 世界上的死亡率。放射治疗 (RT) 通常用于局部晚期患者 疾病。手术治疗后局部晚期 HNSCC 的历史 5 年总生存率， 化疗和放疗约为 50%。许多这些患者在初始治疗后复发和/或发生转移 这些患者的预后仍然很差，中位生存期为 6 至 12 个月。 使用抗 PD-1 抗体进行免疫治疗的缓解率低于 20%。因此，迫切需要 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、 雷西莫特。瑞西莫特比 FDA 批准的咪喹莫特更有效且具有更好的生物利用度 免疫调节药物。 CureBiotech 开发了一种创新的瘤内控释制剂 瑞西莫德 CB101，它使用聚合物基质将药物隔离到局部位点，目的是 避免全身不良免疫反应。与未配制的药物相比，它显示出优越的治疗效果 瑞喹莫德在多个临床前模型中的应用。局部晚期或复发的 HNSCC 很容易被诊断为 瘤内注射CB101。我们假设 CB101 将显着增强癌症对 通过调节肿瘤微环境（TME）进行放疗。在目标 1 中，我们将优化剂量和治疗方案 CB101 和 RT 在 HNSCC 临床前模型中的应用。由于 RT 可能会增加肿瘤细胞上的 PD-L1 表达，因此 目标2，我们将研究抗PD-1抗体与CB101/RT组合的治疗效果。我们 预计较低剂量的 CB101 放疗可能会产生与单独较高剂量放疗相同或更好的结果 但毒性降低，使放疗耐药肿瘤敏感并增强放疗的远隔效应。 这些目标的成功完成将直接影响未来临床试验的设计。我们有 快速、细致地实现这些目标的科学和人员能力。生成的数据在 该项目将被纳入针对 HNSCC 患者的 CB101/RT I 期临床试验的 IND 申请中 FDA。