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申请编号1121483 项目摘要 头颈部鳞状细胞癌（HNSCC）是与癌症有关的第七个主要原因 世界上的死亡率。放射疗法（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年总体存活率， 化学疗法，RT约为50％。这些患者中的许多初次治疗和/或发展转移性后复发 疾病，这些患者的预后仍然很差，中位存活率在6到12个月之间。 抗PD-1抗体的免疫疗法的反应率小于20％。因此，有一个紧迫的 为复发和/或转移性HNSCC患者开发替代方法的临床需求。 Curebiotech Inc.是一家临床前舞台生物技术公司，专注于类似Toll的受体7​​/8激动剂， Resiquimod。 resiquimod比imiquimod更有效，并且具有更好的生物利用度 免疫调节药物。 Curebiotech开发了一种创新的肿瘤内控制释放配方 resiquimod，cb101，它使用聚合物基质将药物隔离到局部部位，目的是 避免系统性不良免疫反应。它显示出优于未形成的效果 在多个临床前模型中的重新词。本地高级或复发的HNSCC可以轻松访问 肿瘤内注射CB101。我们假设CB101将大大增加癌症对 RT通过调节肿瘤微环境（TME）。在AIM 1中，我们将优化剂量和治疗时间表 HNSCC临床前模型中的CB101和RT的of。由于RT可能会增加肿瘤细胞上的PD-L1表达，因此 AIM 2，我们将研究具有CB101/RT组合的抗PD-1抗体的治疗功效。我们 预计使用CB101的较低剂量的RT可能会产生与仅较高剂量辐射相同或更好的结果 但是，随着毒性降低，使RT抗性肿瘤敏感并增强了RT的潜线作用。 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 实现这些目标的科学和人员能力是快速而精心的。生成的数据 该项目将包括在HNSCC患者中CB101/RT的I期临床试验的IND应用中 FDA。