Optimizing Radiosynthetic Yield of [18F]FTT For Wide-Spread Distribution

优化 [18F]FTT 的放射合成产量以实现广泛分布

• 批准号: 10821733
• 负责人: Hsiaoju Sharon Lee
• 金额: $ 104.39万
• 依托单位: TREVARX BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10821733
• 关键词: Binding; Biological Assay; Breast; Cancer Patient; Clinical Trials; Cyclic GMP; Databases; Development; Drug Formulations; Drug Stability; Ensure; Formulation; Foundations; Gene Mutation; Genes; Genomics; Image; Industry; Label; Lead; Malignant Neoplasms; Malignant neoplasm of ovary; Marketing; Measures; Methods; Modeling; Monitor; Multi-Institutional Clinical Trial; Multicenter Trials; Ovarian; Patient imaging; Pennsylvania; Performance; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Poly(ADP-ribose) Polymerase Inhibitor; Polymerase; Positron-Emission Tomography; Preparation; Procedures; Process; Production; Prostate; Proteins; Radiolabeled; Radiopharmaceuticals; Reagent; Recommendation; Sampling; Site; Small Business Technology Transfer Research; Specific qualifier value; Standardization; Technology Transfer; Testing; Tissues; Tracer; Translating; Universities; Writing; analog; clinical center; clinical translation; commercialization; companion diagnostics; design; efficacy trial; imaging biomarker; improved; in vivo; inhibitor; inhibitor therapy; innovation; malignant breast neoplasm; novel; performance site; phase 2 study; phase II trial; phase III trial; pre-Investigational New Drug meeting; precision oncology; predictive marker; protein expression; quantitative imaging; radiotracer; repaired; response; success; supply chain; targeted treatment; timeline; tumor; uptake

ABSTRACT: Poly (ADP-ribose) polymerase inhibitors (PARPi’s) have emerged as important therapeutic agents targeting a broadening class of gene mutations approved for treatment of breast, ovarian, prostate, and other cancers. Genomic assays of BRCA-related genes and tumor homologous repair deficiency are used as companion diagnostics for PARPi therapy but have imperfect predictive efficacy for PARPi response. Trevarx Biomedical Inc.’s (Trevarx) product, [18F]Fluorthanatrace ([18F]FTT), a PET-radiolabeled analog of the PARPi, rucaparib, provides quantitative images of regional PARP expression and drug engagement for all approved PARPi’s. It can thus serve as a PARPi companion diagnostic to identify those most likely to respond to PARPi therapy, and importantly, those unlikely to respond. Over 175 patients imaged in single center clinical trials support the accuracy of [18F]FTT tumor uptake as an in-vivo measure of regional PARPi drug binding, and as an effective imaging-based biomarker of PARP-1 protein levels. A pre-IND meeting with FDA suggested that approval would require: (1) a Phase 3 tissue correlating [18F]FTT uptake and PARP-1 protein expression in tumor samples and (2) multi-center Phase 2 studies of [18F]FTT’s accuracy in predicting PARPi response. A 3-center Phase 2 trial PET-tissue comparison study has been initiated as a pilot for the larger Phase 3 trial, and striking new single- center Phase 2 results on [18F]FTT predictive accuracy strongly support Phase 2 multi-center trials under development. The focus of this proposal is to establish wide-spread radiopharmaceutical supply to support the expanded multi-center trials needed for approval and subsequent clinical translation. With a 3 year competitive lead, [18F]FTT is projected to enter a Phase 3 tracer-tissue trial and multi-center Phase 2 predictive efficacy trials to support an NDA in 2025. The steps described in this project will reduce the extended timeline for FDA approval that has been observed with previous PET radiotracers. Building on the success of our Phase I STTR project (1R41CA2612590-01), this STTR Phase II proposal by Trevarx and Penn will minimize this timeline by establishing methods for unifying radiosynthesis, maximizing product consistency and production yield, and generating a database to manage a larger supply chain for [18F]FTT. We aim to establish a new paradigm for rapid commercialization of PET radiopharmaceuticals by providing a “best practice” template by combining efforts in academic centers and commercial radiopharmaceutical supplier prior to Phase 3 to efficiently bring a novel PET radiotracer to market. Our STTR Phase II proposal establishes a roadmap to move from a single center academic trial to Phase 3 multi-center trials to efficient cGMP commercial production upon NDA approval. In this revised application, we provide more details on [18F]FTT production ( i.e., synthesis kit development and product formulation) and our strategy for the combined academic/commercial rollout of our radiotracer to prepare for the Phase 3 multi-center clinical trial recommended by the FDA in our Pre-IND meeting.

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