Development Therapeutics Branch Clinical Trials

开发治疗分支临床试验

• 批准号: 10926304
• 负责人: YVES POMMIER
• 金额: $ 21.01万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926304
• 关键词: ATR gene; Adrenocortical carcinoma; Camptothecin; Cell Cycle Checkpoint; Chromatin; Clinic; Clinical Trials; Combined Modality Therapy; DNA Damage; DNA Repair; DNA Sequence Alteration; DNA biosynthesis; Defect; Drug Kinetics; Drug Targeting; Epigenetic Process; Genome; Genomic Instability; Genomics; H2AFX gene; Immune checkpoint inhibitor; Inpatients; Malignant Neoplasms; Malignant neoplasm of prostate; Malignant neoplasm of thorax; Malignant neoplasm of urinary bladder; Metabolic; Molecular Target; Multicenter Studies; Patients; Pharmacodynamics; Phase; Phase I Clinical Trials; Phase I/II Trial; Pilot Projects; Poly(ADP-ribose) Polymerases; Randomized; Recruitment Activity; Refractory; Relapse; Running; Safety; Small Cell Carcinoma; Solid; Solid Neoplasm; Testing; Tissue Procurements; Topoisomerase Inhibitors; Topoisomerase-I Inhibitor; Topotecan; Type I DNA Topoisomerases; clinical development; expiration; genomic signature; hospice environment; immune checkpoint; inhibitor; kinase inhibitor; molecular marker; nanoparticle; neuroendocrine cancer; novel; novel therapeutic intervention; open label; pharmacodynamic biomarker; phase II trial; pre-clinical; response; safety assessment; small cell lung carcinoma; targeted delivery; temozolomide; therapeutic development; tumor

We focus on drugs targeting the genome, especially novel topoisomerase inhibitors as single agents and in combination with DNA repair and immune checkpoint inhibitors. One of our topoisomerase I (TOP1) inhibitors, LMP400 (Indotecan) finished Phase 1 clinical trials. Another (LMP776, Indimitecan) is finishing phase 1 and LMP744 is in phase 1. We have clinical trials with tumor-targeted TOP1 inhibitors (Onivyde, CRLX101, PLX-038 and PEN-866), and clinical trials with combination of TOP1 inhibitors with ataxia-telangiectasia and rad3-related (ATR), poly(ADPribose)polymerase (PARP1/2) and immune checkpoint inhibitors. Our ongoing clinical trials include: Actively recruiting: 13C0131: A Pilot Study of Inpatient Hospice with Procurement of Tissue on Expiration in Thoracic Malignancies; 15C0150: A Phase I/II Trial of Topotecan with VX-970 (M6620), an ATR Kinase Inhibitor in Small Cell Cancers; 16C0107: A Phase I/II Trial of CRLX101, a Nanoparticle Camptothecin with Olaparib in Patients with Relapsed/Refractory Small Cell Lung, Bladder and Prostate Cancers; 17C0117: A Phase 1/2a, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of PEN-866 in Advanced Solid Malignancies; 18C0110: Safety Run-In and Phase II Trial of M7824 and Topotecan or Temozolomide in Relapsed Small Cell Cancers; 20C0009: Randomized Phase II Trial of Topotecan Plus M6620 (VX-970) vs. Topotecan Alone in Patients with Relapsed Small-Cell Lung Cancer; 20C0013: Phase I/II trial of PLX038 (PEGylated SN38) and Rucaparib in Solid tumors and Small Cell Cancers;17C0012: Ph I MM-398 plus Veliparib.

我们专注于针对基因组的药物，特别是作为单一药物以及与 DNA 修复和免疫检查点抑制剂组合的新型拓扑异构酶抑制剂。我们的拓扑异构酶 I (TOP1) 抑制剂之一 LMP400 (Indotecan) 已完成 1 期临床试验。另一个（LMP776、Indimitecan）正在完成 1 期，LMP744 正处于 1 期。我们有肿瘤靶向 TOP1 抑制剂（Onivyde、CRLX101、PLX-038 和 PEN-866）的临床试验，以及 TOP1 抑制剂与共济失调毛细血管扩张症和 rad3 相关 (ATR)、聚 (ADP 核糖)聚合酶(PARP1/2) 和免疫检查点抑制剂。我们正在进行的临床试验包括： 积极招募：13C0131：胸部恶性肿瘤过期组织采购住院临终关怀试点研究； 15C0150：拓扑替康与 VX-970 (M6620)（一种 ATR 激酶抑制剂）治疗小细胞癌的 I/II 期试验； 16C0107：CRLX101（一种纳米颗粒喜树碱与奥拉帕尼）在复发/难治性小细胞肺癌、膀胱癌和前列腺癌患者中的 I/II 期试验； 17C0117：一项 1/2a 期、开放标签、多中心研究，旨在评估 PEN-866 在晚期实体恶性肿瘤中的安全性、耐受性、药代动力学、药效学和初步抗肿瘤活性； 18C0110：M7824 和拓扑替康或替莫唑胺治疗复发性小细胞癌的安全性磨合和 II 期试验； 20C0009：拓扑替康加 M6620 (VX-970) 与单独拓扑替康在复发性小细胞肺癌患者中的随机 II 期试验； 20C0013：PLX038（聚乙二醇化SN38）和Rucaparib治疗实体瘤和小细胞癌的I/II期试验；17C0012：I期MM-398加Veliparib。

项目成果

Small cell lung cancer: Time to revisit DNA-damaging chemotherapy.

小细胞肺癌：是时候重新审视 DNA 损伤性化疗了。

• 发表时间: 2016
• 影响因子: 17.1
• 作者: Thomas, Anish;Pommier, Yves
• 通讯作者: Pommier, Yves

Whole-exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable response to DNA repair-targeted therapies.

全外显子组测序揭示了种系突变的小细胞肺癌亚型，对 DNA 修复靶向治疗有良好的反应。

• 发表时间: 2021
• 影响因子: 17.1
• 作者: Tlemsani, Camille;Takahashi, Nobuyuki;Pongor, Lorinc;Rajapakse, Vinodh N;Tyagi, Manoj;Wen, Xinyu;Fasaye, Grace;Schmidt, Keith T;Desai, Parth;Kim, Chul;Rajan, Arun;Swift, Shannon;Sciuto, Linda;Vilimas, Rasa;Webb, Santhana;Nichols, Samant
• 通讯作者: Nichols, Samant

BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers.

BRCAness、SLFN11 和 RB1 缺失可预测三阴性乳腺癌对拓扑异构酶 I 抑制剂的反应。

• 发表时间: 2020
• 影响因子: 17.1
• 作者: Coussy, Florence;El;Château;Dahmani, Ahmed;Montaudon, Elodie;Leboucher, Sophie;Morisset, Ludivine;Painsec, Pierre;Sourd, Laura;Huguet, Léa;Nemati, Fariba;Servely, Jean;Larcher, Thibaut;Vacher, Sophie;Briau
• 通讯作者: Briau

Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11.

使用针对复制压力、ATR 和 Schlafen 11 的药物进行精准肿瘤学。

• 发表时间: 2021-09-14
• 影响因子: 5.2
• 作者: Jo, Ukhyun;Murai, Yasuhisa;Takebe, Naoko;Thomas, Anish;Pommier, Yves
• 通讯作者: Pommier, Yves

Response to Letter to the Editor by Yang et al.

对杨等人给编辑的信的回应。

• 发表时间: 2020-06
• 作者: Hassan, Raffit;Sengupta, Manjistha;Murai, Junko;Pommier, Yves
• 通讯作者: Pommier, Yves