Breast Cancer PARP PET Imaging AIP to Support FDA Approval & Commercialization

乳腺癌 PARP PET 成像 AIP 支持 FDA 批准

• 批准号: 10183011
• 负责人: Sean Denis Carlin
• 金额: $ 63.11万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-24 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10183011
• 关键词: Autoradiography; BRCA mutations; Binding; Biological Assay; Biological Markers; Breast; Cancer Center; Cancer Patient; Chemistry; Clinical Data; Clinical Trials; Data; Defect; Development; Diagnosis; Diagnostic; Elements; Formalin; Freezing; Future; Gene Mutation; Image; Immunofluorescence Immunologic; Immunohistochemistry; In Vitro; Label; Lead; Licensing; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Methodology; Methods; Multicenter Trials; Ovarian; PET/CT scan; Paraffin Embedding; Patients; Pennsylvania; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase III Clinical Trials; Poly(ADP-ribose) Polymerases; Polymerase; Positron-Emission Tomography; Principal Investigator; Production; Prostate; Protocols documentation; Radiopharmaceuticals; Reference Standards; Research; Site; Standardization; Testing; Time; Tissue Embedding; Tissues; Toxic effect; Tracer; Universities; Validation; Washington; analog; base; clinical translation; commercialization; design; diagnostic accuracy; homologous recombination; imaging biomarker; improved; in vivo; industry partner; inhibitor/antagonist; malignant breast neoplasm; mutation assay; neoplastic cell; novel therapeutics; phase 3 study; phase II trial; phase III trial; predicting response; programs; prospective; targeted treatment; trial comparing; trial design; tumor; uptake

Abstract: Poly (ADP-ribose) polymerase (PARP) inhibitor drugs (PARPi's) have emerged as important new therapeutic agents targeting a broadening class of gene mutations present in breast, ovarian, prostate and a host of other cancers. Identification of patients who might benefit from PARPi's has relied on assays for defects in homologous recombination (HRD), such as BRCA1/2 mutations, but these assays have been imperfect predictors of response to PARPi's. Drug binding to PARP1 present in tumor cells is a common and necessary factor for effective PARPi therapy. [18F]fluorthanatrace (FTT) is a PET-labeled analog of the PARPi rucaparib, and early clinical data in ovarian and breast cancer trials support [18F]FTT tumor uptake as an in-vivo measure of regional PARP1 drug binding, and indicate the potential of [18F]FTT PET as a PARPi predictive imaging biomarker. [18F]FTT could therefore provide benefits for patients with breast and other cancers by identifying those most likely to respond to PARPi therapy, while sparing those who will not respond from toxicity, unnecessary expense, and wasted time. To further the development, clinical translation, and commercialization of [18F]FTT, we propose an Academic Industrial Partnership (AIP) comprised of The University of Pennsylvania ((Penn), lead academic partner), MD Anderson Cancer Center(MDACC), and Washington University (WU) with Trevarx Biomedical, Inc (Trevarx). Trevarx, a radiopharmaceutical corporation with the exclusive license for [18F]FTT, is developing [18F]FTT as an imaging biomarker to guide PARPi treatment, with a first indication in breast cancer. Based on discussions with the FDA and advisors, [18F]FTT approval will require a Phase 3 study of the accuracy of [18F]FTT PET/CT for diagnosing PARP1 expressing cancer. The aims of this AIP proposal focus on critical components necessary for a Phase 3 trial for [18F]FTT FDA approval: (1) a Trevarx-held IND with standardized tracer production methodology and product specification; (2) validation of an immunohistochemistry (IHC) assay of PARP1 expression in formalin-fixed paraffin embedded (FFPE) tissue as a reference standard for [18F]FTT PET diagnostic accuracy; and (3) a Phase 2 multi-center trial to test and validate methods in a multi-center setting and provide preliminary data to design the pivotal Phase 3 trial. Completion of the these aims will enable a Phase 3 trial to support [18F]FTT FDA approval, commercial supply of [18F]FTT, and ongoing research by the academic partners to document the value of [18F]FTT PET/CT for guiding PARPi treatment, including prospective multi- center biomarker-focused studies.

抽象的： 聚（ADP-核糖）聚合酶（PARP）抑制剂药物（PARPI）已经出现了重要的新治疗 针对乳房，卵巢，前列腺和其他许多其他基因突变的代理 癌症。鉴定可能从Parpi受益的患者依赖于同源缺陷的测定 重组（HRD），例如BRCA1/2突变，但是这些测定是不完美的响应预测指标 到Parpi的。药物与肿瘤细胞中存在的PARP1结合是有效PARPI的常见和必要因素 治疗。 [18F] Fluorthanatrace（FTT）是parpi rucaparib的宠物标记的类似物，也是早期的临床数据 卵巢癌和乳腺癌试验支持[18F] FTT肿瘤吸收作为区域性PARP1药物的体内量度 结合，并表明[18F] ftt PET作为PARPI预测成像生物标志物的潜力。 [18f] ftt可以 因此，通过识别最有可能反应的人，为患有乳腺癌和其他癌症患者提供福利 在保留那些不会因毒性，不必要的费用和浪费的人做出回应的人时， 时间。 为了进一步发展[18f] ftt的发展，临床翻译和商业化，我们提出了一个学术 工业合作伙伴关系（AIP）由宾夕法尼亚大学（（Penn），主要学术合作伙伴）组成 安德森癌症中心（MDACC）和华盛顿大学（WU）与Trevarx Biomedical，Inc（Trevarx）。 Trevarx是一家具有[18F] FTT独家许可的放射性药物公司，正在开发[18f] ftt作为一个 成像生物标志物以指导PARPI治疗，并在乳腺癌中首次指示。基于与 FDA和顾问，[18F] FTT批准将需要[18F] FTT PET/CT的准确性3期研究 诊断表达癌症的PARP1。该AIP提案的目的集中于所需的关键组成部分 [18F] FTT FDA批准的3阶段试验：（1）具有标准化示踪剂生产的Trevarx-Held Ind 方法和产品规范； （2）验证PARP1的免疫组织化学（IHC）测定 在福尔马林固定石蜡嵌入（FFPE）组织中的表达作为[18F] ftt PET的参考标准 诊断准确性； （3）在多中心设置中测试和验证方法的2阶段多中心试验 并提供初步数据来设计关键阶段3期试验。这些目标的完成将使一个阶段 3试验，以支持[18F] FTT FDA批准，[18F] FTT的商业供应以及学术的持续研究 记录[18F] ftt PET/CT的价值用于指导PARPI治疗的价值，包括 中心以生物标志物为中心的研究。