Phase 1 cross over biodistribution study of [203Pb]VMT01 for single photon emission computed tomography (SPECT) and [68Ga]VMT02 for positron emission tomography (PET) imaging of stage 4 melanoma

用于单光子发射计算机断层扫描 (SPECT) 的 [203Pb]VMT01 和用于 4 期黑色素瘤正电子发射断层扫描 (PET) 成像的 [68Ga]VMT02 的第 1 期交叉生物分布研究

• 批准号: 10021596
• 负责人: FRANCES L JOHNSON
• 金额: $ 102.39万
• 依托单位: VIEWPOINT MOLECULAR TARGETING, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-19 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021596
• 关键词: Adult; Agreement; Authorization documentation; Biodistribution; Biopsy; Calibration; Chemistry; Clinic; Clinical; Clinical Data; Clinical Trials; Computer software; Contracts; Data; Discipline of Nuclear Medicine; Documentation; Dose; Effectiveness; Enrollment; Equipment and Supplies; FDA approved; Funding; Future; Gender; Goals; Human; Human Resources; Image; Immunotherapy; Incidence; Injections; Institutional Review Boards; Investigational New Drug Application; Investments; Iowa; Lead; Letters; Licensing; Malignant Neoplasms; Medical; Medical Imaging; Melanocortin 1 Receptor; Metastatic Melanoma; Modeling; Mus; New Mexico; Organ; Outcome; Patient Selection; Patient-Focused Outcomes; Patients; Peptides; Pharmaceutical Preparations; Phase; Positron-Emission Tomography; Procedures; Production; Protocols documentation; Publications; Published Comment; Publishing; Pyrogens; Qualifying; Quality of life; Radiolabeled; Radionuclide therapy; Radiopharmaceuticals; Randomized; Resistance; Running; Safety; Scanning; Secure; Site; Small Business Innovation Research Grant; Sterility; Therapeutic; Therapy Clinical Trials; Therapy trial; Training; Universities; X-Ray Computed Tomography; base; clinical research site; clinical trial enrollment; companion diagnostics; data management; design; dosimetry; first-in-human; human imaging; human subject; improved outcome; kernel methods; meetings; melanoma; particle; particle therapy; phase I trial; pre-clinical; preclinical study; primary outcome; response; side effect; single photon emission computed tomography; statistics; treatment planning; tumor

SIGNIFICANCE: Melanoma incidence is rising faster than any other cancer and metastatic melanoma is typically fatal. Responses to targeted and immunotherapies can be remarkable, but low response rates, acquired resistance, and adverse side effects limit long-term quality of life for these patients. The overall response rate to all therapies remains dismally near 50% and the 5-year survival is <25%. Preclinical studies have identified radiolabeled peptides that target the melanocortin receptor 1 (MC1R) as a potential therapeutic alternative. While this approach using -particle emitters has been largely ineffective preclinically, previous publications and our Phase I data have demonstrated efficacy of Viewpoint’s MC1R-targeted VMT01 -particle therapy in mice bearing melanoma tumors. Thus, VMT01 is designed to meet the significant unmet medical need to improve outcomes for these patients (initial indication of progressive stage 4 metastatic melanoma), with potential for expanded indications in combination with FDA-approved melanoma drugs (e.g., immunotherapies). In this revised Phase II SBIR project, Viewpoint will complete a Phase 1 first-in-human clinical trial to determine the safety of its companion diagnostics. It is further expected that the company will have gained a preliminary understanding of the effectiveness of [68Ga]VMT02 imaging (PET) to identify MC1R positive tumors and the utility of [203Pb]VMT01 imaging (SPECT) for performing patient dosimetry for personalized [212Pb]VMT01 -therapy. PREDICATE PHASE I MILESTONES include: efficacy (therapy and imaging) in mice; pharm/tox of lead VMT01; automated radiopharmaceutical production with GMP kits; exclusive licenses to IP; clinical consortium with Mayo Clinic and 203Pb supply with Lantheus Medical Imaging; CRO for statistics/clinical data (Compleware, Inc.); and a radiopharmacy partner (Hotshots Nuclear Medicine) for manufacturing/distribution of [203Pb]VMT01. EQUITY INVESTMENTS: Viewpoint has secured $650,000 in equity investment to establish manufacturing of 212Pb generators for future clinical therapy trials. The company will complete the following Aims toward its goals. AIM 1. Secure FDA “safe to proceed” designation to conduct the Phase 1 imaging trial of [203Pb]VMT01 and [68Ga]VMT02 under IND. AIM 2. Complete a Phase 1 safety and biodistribution study of [203Pb]VMT01 and [68Ga]VMT02 imaging in human subjects and demonstrate their utility for identifying MC1R positive tumors and performing patient-specific dosimetry. OUTCOMES: We expect to demonstrate the clinical safety of [203Pb]VMT01 and [68Ga]VMT02. We further expect to develop preliminary understanding of the efficacy of [68Ga]VMT02 PET/CT to identify MC1R+ tumors and the utility of [203Pb]VMT01 SPECT/CT for patient-specific dosimetry for [212Pb]VMT01 -therapy. Thus, we will be prepared to initiate dosimetry-based trials of [212Pb]VMT01 -particle therapy for metastatic melanoma to be funded under Phase IIB SBIR studies and Phase III equity investments.

意义：黑色素瘤发病率的上升速度比其他任何癌症都快，转移性黑色素瘤是典型的 致命的。对靶向和免疫疗法的反应可能很显著，但获得性应答率较低 耐药性和副作用限制了这些患者的长期生活质量。总体应答率 所有疗法都保持在令人沮丧的接近50%的水平，5年存活率为25%。临床前研究已经确定 靶向黑素皮质素受体1(MC1R)的放射性标记多肽，作为潜在的治疗替代方案。而当 这种使用粒子发射器的方法在临床前基本上是无效的，以前的出版物和我们的 I期数据显示，视点公司的MC1R靶向VMT01VMT01VMT01颗粒治疗在小鼠中有效 患有黑色素瘤。因此，VMT01旨在满足未得到满足的重大医疗改进需求 这些患者的预后(进展期4期转移性黑色素瘤的初步指征)，具有潜在的 扩大适应症，与FDA批准的黑色素瘤药物(如免疫疗法)相结合。在这 修订的第二阶段SBIR项目，观察点将完成第一阶段的首个人类临床试验，以确定 其配套诊断的安全性。进一步预计，该公司将获得初步的 [68Ga]VMT02显像(PET)识别MC1R阳性肿瘤的有效性及其应用的认识 用于个人化[212Pb]VMT01治疗的患者剂量测量。 预测的第一阶段里程碑包括：小鼠的疗效(治疗和成像)；铅的药效/毒性 VMT01；使用GMP试剂盒的自动化放射性药物生产；IP的独家许可证；临床联盟 梅奥诊所和兰修斯医学成像公司提供的203Pb；CRO用于统计/临床数据(Compleware， Inc.)；以及制造/分销[203Pb]VMT01的放射性药物合作伙伴(Hotshot核医学)。 股权投资：视点已获得65万美元的股权投资，以建立制造 用于将来的临床治疗试验的212个铅发生器。公司将朝着目标完成以下目标。 目标1.确保FDA获得进行[203Pb]VMT01第一阶段成像试验的安全许可 和[68Ga]VMT02。 目的2.完成[203Pb]VMT01和[68Ga]VMT02显像的一期安全性和生物分布研究 并展示了它们在识别MC1R阳性肿瘤和进行 特定于患者的剂量测定。 结果：我们期望证明[203Pb]VMT01和[68Ga]VMT02的临床安全性。我们进一步期待 初步了解[68Ga]VMT02PET/CT鉴别MC1R+肿瘤的疗效 [~(203)Pb]VMT01 SPECT/CT在[~(212)Pb]VMT01治疗中的应用因此，我们将成为 准备启动基于剂量学的[212Pb]VMT01颗粒治疗转移性黑色素瘤的试验 在第二阶段B SBIR研究和第三阶段股权投资项下提供资金。