177Lu-Pentixather(177Lu-Pentixather) - 药物靶点：CXCR4_在研适应症：急性白血病，多发性骨髓瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

CXCR4

作用方式

拮抗剂

作用机制

CXCR4拮抗剂(C-X-C基序趋化因子受体4拮抗剂)

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病

在研适应症

急性白血病多发性骨髓瘤

非在研适应症-

原研机构

Julius-Maximilians-Universität Würzburg

在研机构

Nantes University Hospital

非在研机构-

权益机构-

最高研发阶段临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

2

项与 177Lu-Pentixather 相关的临床试验

CTIS2022-501019-15-00

/ Recruiting临床1/2期IIT

- RC20_0123

开始日期-

申办/合作机构-

NCT06356922

/ Recruiting临床1/2期IIT

Phase I/II Study Assessing Radioligand Therapy (RLT) Using [177Lu]Lu-PentixaTher for Relapsed/refractory CXCR4+ Acute Leukemia.

CXCR4 inhibition may represent a new therapeutic strategy in acute leukemia (AL) patients, not only by increasing chemosensitivity but also by preventing relapse of the disease by disruption of the interaction of residual leukemic cells with the bone marrow niche. Radiolabeled CXCR4 ligands have been developed for PET imaging (68Ga-PentixaFor; INN: Gallium (68Ga) boclatixafortide) and radioligand therapy (RLT) ([177Lu]Lu-PentixaTher/[90Y]Y-PentixaTher). [177Lu]Lu and [90Y]Y-PentixaTher have been tested in three multiple myeloma patients in named-patient use with a remarkable efficacy in 2 patients (Herrmann, 2016). Moreover, feasibility of CXCR4 PET imaging in AML was reported, providing a framework for future theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche (Herhaus, 2016).
Here a Phase I/II study to determine maximal tolerated dose (MTD) of a RLT using [177Lu]Lu-PentixaTher in relapsed/refractory AL was designed. This will be a standard phase I/II 3+3 dose escalation study. Five dose levels will be tested, so 6 to 21 patients have to be included in the study.

开始日期2024-10-22

申办/合作机构

Nantes University Hospital

100 项与 177Lu-Pentixather 相关的临床结果

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100 项与 177Lu-Pentixather 相关的转化医学

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100 项与 177Lu-Pentixather 相关的专利（医药）

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9

项与 177Lu-Pentixather 相关的文献（医药）

2025-01-01·Theranostics

CXCR4-directed endoradiotherapy with [¹⁷⁷Lu]Pentixather added to total body irradiation for myeloablative conditioning in patients with relapsed/refractory acute myeloid leukemia

Article

作者: Weber, Wolfgang ; Verbeek, Mareike ; Eiber, Matthias ; Allmann, Anne ; Koch, Katrin ; Herhaus, Peter ; Nickel, Katharina ; Braitsch, Krischan ; Hefter, Maike ; D'Alessandria, Calogero ; Brosch-Lenz, Julia ; Bassermann, Florian ; Götze, Katharina S ; Peeken, Jan C ; Rudelius, Martina ; Lorenzini, Theo

Rationale: Despite recent advances in the targeted therapy of AML, the disease continues to have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (alloSCT) remains to be the curative therapy option for fit patients with high-risk disease. Especially patients with relapsed or refractory (r/r) AML continue to have poor outcomes. Myeloablative total body irradiation (TBI) based conditioning can be used in AML patients refractory to multiple lines of standard therapy, but the optimal conditioning regimen remains unclear for patients considered to be chemotherapy- refractory. Feasibility of C-X-C-motif chemokine receptor 4 (CXCR4)-directed endoradiotherapy (ERT) has previously been demonstrated in AML patients with CXCR4 expression on leukemic blasts. Methods: Here, we report on a small cohort of seven AML patients refractory to multiple lines (range 3-7) of therapy, who received CXCR4-directed ERT with [¹⁷⁷Lu]Pentixather in combination with TBI and chemotherapy prior to alloSCT. We report outcomes with a focus on toxicity, engraftment, the impact on the bone marrow (BM) niche and efficacy. Results: In this intensively pre-treated group of patients, promising response (6 out of 7 patients) and engraftment (6 out of 7 patients) rates were observed. Histopathological analysis showed that niche compartments are spared and allow for engraftment to occur despite the combined ERT and TBI conditioning. Conclusion: To the best of our knowledge, we report on the first seven patients who received CXCR4-directed ERT in sequential combination with TBI and chemotherapy, providing an effective, individualized conditioning regimen for intensively pre-treated r/r AML patients.

2023-11-21·Radiation Research

Chemokine Receptor CXCR4 Radioligand Targeted Therapy Using 177Lutetium-pentixather for Pulmonary Neuroendocrine Cancers

Article

作者: Tomanek-Chalkley, Ann M. ; Rastogi, Prerna ; Bellizzi, Andrew M. ; Fath, Melissa A. ; Menda, Yusuf ; Graves, Stephen A. ; Ewald, Jordan T. ; Howe, James R. ; O'Dorisio, M Sue ; Liu, Dijie ; O'Dorisio, Thomas M. ; Spitz, Douglas R. ; Robles-Planells, Claudia

Intermediate to high-grade lung neuroendocrine tumors (NETs; i.e., atypical carcinoid tumors) and neuroendocrine carcinomas (NECs) are currently difficult to cure. These tumors were found to express the CXCR4 G-protein coupled receptor that can be targeted with radioligands. PCR and flow cytometric analysis of lung NET and NEC cell lines using an anti-CXCR4 antibody demonstrated that all cell lines tested expressed CXCR4. PET/CT imaging with 68Galium-pentixafor in mouse xenografts of NETs and NECs verified tumor targeting that was blocked by a CXCR4 agonist. Clonogenic survival analysis demonstrated a more than additive enhancement of killing when 1 μM auranofin (a thioredoxin reductase inhibitor) was used as a radiosensitizer in combination with 177Lu-pentixather (10 μCi). DMS273 small cell lung cancer xenografts in female nude mice treated with 25 μCi/g 177Lu-pentixather induced inhibition of tumor growth and resulted in an increase in overall survival without causing unacceptable normal tissue toxicities. Immunohistochemical staining of 95 retrospective human samples (containing 90 small cell lung carcinomas) demonstrated 84% CXCR4 positivity. In a multivariable analysis of this cohort that included age, gender, stage, primary site, SSTR2 status, and CXCR4 status, Cox regression models determined that only distant metastasis at presentation (P < 0.01) and a CXCR4 H-score >30 (P = 0.04) were significantly associated with reduced survival. Prospective clinical testing of patient tumors identified CXCR4-positivity in 76% of 21 NECs, 67% of 15 lung NETs (including 8 of 10 atypical carcinoids), and 0% of 25 non-lung NETs (including 5 NETS G3s). These data support the hypothesis that CXCR4-targeted theranostics can be utilized effectively for select NETs and NECs.

2023-04-01·Mini-Reviews in Medicinal Chemistry

Nuclear Medicine Application of Pentixafor/Pentixather Targeting CXCR4 for Imaging and Therapy in Related Disease

Review

作者: Xue, Qianqian ; Chen, Zhenying ; Yao, Shaobo

:C-X-C-motif chemokine receptor 4 (CXCR4) is a novel predictive biomarker for metastasis and poor prognosis in individuals with malignancies. CXCL12 is the only cognate ligand of CXCR4. CXCL12/CXCR4 signaling pathways are involved in the cross-talk among cancer cells, T cells, stromal cells, and their microenvironments, including the regulation and direction of T cell migration (chemotaxis), proliferation, and differentiation of immature progenitor stem cells. As CXCR4 overexpression is related to tumor prognosis, it is essential to quantitatively evaluate CXCR4 expression levels in vivo.:68Ga-Pentixafor, as a radiolabeled tracer, shows high specificity and affinity for CXCR4 in tumors. Thus, CXCR4-directed imaging with 68Ga-Pentixafor has been investigated to evaluate CXCR4 expression in patients non-invasively. In recent years, many small cohorts, including those of individuals with hematologic malignancies, solid tumors, and cardiovascular and infectious diseases, have been reported. So far, 68Ga-Pentixafor has been used successfully in individuals with hematologic malignancies. In addition, Lutetium-177 (177Lu) or Yttrium-90 (90Y)-labeled Pentixather (an analog of Pentixafor) suggested high potential applicability in tumor endoradiotherapy (ERT) with CXCR4 overexpression. Patients with advanced-stage multiple myeloma, refractory acute leukemia, and diffuse large B-cell lymphoma received a certain amount of 177Lu-Pentixather or 90Y-Pentixather. This review aimed to overview the current CXCR4-directed positron emission computed tomography (PET) molecular imaging based on Pentixafor in several diseases and ERT.

100 项与 177Lu-Pentixather 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性白血病	临床2期	法国	Nantes University Hospital	2024-10-22
多发性骨髓瘤	临床2期	法国	Nantes University Hospital	2024-10-22

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


P133 (EBMT2022)	N/A	复发性急性髓细胞白血病 CXCR4 expression	6	Chemokine receptor 4 directed endoradiotherapy with [ 177 lu]-pentixather	(鹽夢憲蓋衊遞齋願獵醖) = 獵餘願鹽齋獵繭蓋艱蓋夢顧齋顧範廠廠範鏇觸 (顧齋觸艱積鹹顧構艱憲 ) 更多	-	2022-03-19