124I-cG250 ImmunoPET Imaging of Sunitinib Treatment Response in Renal Cell Cancer

肾细胞癌舒尼替尼治疗反应的 124I-cG250 免疫 PET 成像

• 批准号: 8338883
• 负责人: Steven Mark Larson
• 金额: $ 37.95万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8338883
• 关键词: Abdomen; Accounting; Address; Adverse effects; Antibodies; Antibody Affinity; Antigens; Applications Grants; Benign; Binding; Biological Markers; Cancer Detection; Cessation of life; Characteristics; Chest; Clear Cell; Clinical; Clinical Protocols; Clinical Trials; Clinical Trials Design; Collaborations; Conduct Clinical Trials; Critiques; Data; Detection; Diagnosis; Diagnostic; Diagnostic tests; Dilatation - action; Dose; Ensure; Evaluation; Failure; Genitourinary system; Growth; Histology; Image; Imaging Techniques; Individual; Inflammation; Kidney; Knowledge; Label; Lead; Lesion; Letters; Licensing; Literature; Malignant Neoplasms; Measures; Medical Oncologist; Metastatic Neoplasm to the Bone; Metastatic Neoplasm to the Lung; Metastatic Renal Cell Cancer; Methodology; Monitor; Mus; Neck; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; Patient Selection; Patients; Peer Review; Pelvis; Pharmaceutical Preparations; Pharmacodynamics; Pharmacotherapy; Phase; Pilot Projects; Positron; Positron-Emission Tomography; Protocols documentation; Radiolabeled; Reagent; Regimen; Renal Cell Carcinoma; Renal Mass; Renal carcinoma; Research Personnel; Resistance; Resolution; Safety; Schedule; Signal Transduction; Staging; Systemic Therapy; Testing; Therapeutic Studies; Time; Tissues; Toxic effect; Treatment Protocols; United States; Urinary tract; Urogenital Cancer; X-Ray Computed Tomography; base; bone imaging; cancer diagnosis; carbonate dehydratase; effective therapy; experience; follow-up; imaging modality; improved; in vivo; man; molecular imaging; novel; novel therapeutics; open label; phase 1 study; radiotracer; response; soft tissue; standard of care; therapy resistant; treatment planning; treatment response; tumor; uptake

DESCRIPTION (provided by applicant): Renal cell carcinoma (RCC) is the most common malignancy of the kidney, accounting for more than 58,000 new diagnoses of cancer and 13,000 cancer deaths in the United States during 2010. The central theme of this R21 (PAR 08-147) is to refine the current use of Positron Emission Tomography of 124I-cG250 (ImmunoPET) in RCC as a pharmacodynamic and predictive biomarker during sunitinib targeted drug therapy. This is a resubmission of our prior R21 scored at the 15th percentile. We have addressed the reviewer's critique, based primarily on newly available literature and data from the Phase III Wilex trial. We propose a single center, open-label, investigator-initiated, pilot study of 124I-cG250 imaging in 25 patients with advanced or metastatic clear cell RCC who are scheduled to receive treatment with sunitinib for clinical indications. The 124I-cG250 imaging test x 3 at baseline, during treatment and in follow-up, will be assessed for its ability to predict response i comparison to bone scan, high resolution body CT scan of the chest, abdomen, and pelvis, RECIST version 1.1, time to progression and survival. The trial will be performed in collaboration with Dr. Robert Motzer, Genitourinary medical oncologist, who has pioneered improved targeted drug therapies for RCC. Our core hypothesis is that at baseline, detection of CAIX antigen expression in clear cell renal cancer, based on 124I- cG250 ImmunoPET, will provide improved single test staging in comparison to standard CT and bone scan; Also, ImmunoPET measured changes in 124I-cG250 uptake will provide earlier and more accurate assessment of treatment response in advanced metastatic RCC, in comparison to RECIST 1.1. This R21 grew out of diagnostic and therapeutic studies with radiolabeled G250, in which we and others determined that in vivo targeting in mice and patients bearing clear cell renal cancer resulted in exceptional target to background ratios and % injected dose per gram. Based on this knowledge, we performed a Phase I study with 124I-cG250 for detection of clear-cell renal cancer, hoping to exploit the combination of an exceptional targeting antibody, and the sensitivity and quantitative power of PET imaging, for improved diagnosis in man. The clinical rationale was to characterize non-invasively, the histology of a renal mass and therefore avoid unnecessary renal surgery that could potentially damage kidneys that are often already clinically compromised. The phase I study found the PET imaging approach to be highly effective for the non-invasive diagnosis of clear cell renal cancer (Divgi et al: Lancet Oncol 2007;8:304-10). Subsequently, Wilex Inc, in partnership with IBA US, licensed the approach and has now completed a Phase III pivotal trial with 124I-cG250. Study results are now with the FDA for review. As far as we are aware, this is the first positron labeled antibody that has been manufactured under GMP conditions and submitted for a diagnostic NDA from the FDA. The current proposal is a logical extension of these prior studies and, if successful, will improve staging and monitoring of systemic treatment response in advanced renal cell carcinoma.

描述（由申请人提供）：肾细胞癌（RCC）是肾脏最常见的恶性肿瘤，在2010年占58,000多个新诊断的癌症和13,000例癌症死亡。该R21的中心主题（PAR）（PAR） 08-147）是在RCC中使用124i-CG250（Immunopet）的正电子发射断层扫描的目前用作在Sunitinib靶向药物治疗期间的药效和预测生物标志物。这是我们以前的R21在第15个百分点中得分的重新提交。我们已经讨论了审稿人的批评，主要基于新近可用的文献和III阶段Wilex试验的数据。我们建议对25例晚期或转移性透明细胞RCC患者进行124i-CG250成像的调查人员发射的单个中心，研究人员发射的，试点研究，他们计划接受Sunitinib接受舒尼替尼治疗以进行临床适应症。将评估124i-CG250成像测试X 3，在治疗和随访期间，将评估其预测响应的能力I与骨扫描，高分辨率的身体CT胸部，腹部和骨盆的高分辨率身体扫描，Recist版本，Recist版本1.1，进展和生存的时间。该试验将与Genitiourinary Medical肿瘤学家Robert Motzer博士合作进行，他率先提高了改进的RCC靶向药物疗法。我们的核心假设是，在基线时，基于124i-CG250免疫集的透明细胞肾脏癌中CAIX抗原表达的检测将提供改进的单个测试分期，而不是标准CT和骨扫描。此外，与再生1.1相比，免疫集测量的124i-CG250摄取的变化将提供早期转移性RCC治疗反应的更早，更准确的评估。这种R21从放射性标记的G250进行的诊断和治疗研究中生长出来，在这种研究中，我们和其他人确定，在小鼠和患有明显细胞肾癌的患者中，体内靶向靶向明确的肾癌与背景比率具有出色的靶标和每克注射剂量的特殊剂量。基于这些知识，我们对124i-CG250进行了I阶段研究，以检测清除肾癌，希望利用特殊靶向抗体的组合以及PET成像的灵敏度和定量能力，以改善人体诊断。临床原理是非侵入性的肾脏肿块的组织学表征，因此避免了不必要的肾脏手术，这可能会损害通常在临床上损害的肾脏。第一阶段的研究发现，宠物成像方法对于透明细胞肾癌的非侵入性诊断非常有效（Divgi等：Lancet Oncol 2007; 8：304-10）。随后，Wilex Inc与IBA US合作，获得了该方法的许可，现在已经完成了III期关键试验，其中124i-CG250。现在的研究结果与FDA进行了审查。据我们所知，这是在GMP条件下生产的第一个标志性抗体，并提交了FDA诊断NDA。当前的建议是对这些先前研究的逻辑扩展，如果成功，将改善晚期肾细胞癌中系统治疗反应的分期和监测。