A Phase 1 Study of GRN163L (Imetelstat) in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia That is in Second or Greater Relapse or That is Refractory to Relapse Therapy; Myelodysplastic Syndrome or Juvenile Myelomonocytic Leukemia in First or Greater Relapse or is Refractory to Relapse Therapy

This phase I trial tests the safety, side effects, and best dose of imetelstat in combination with fludarabine and cytarabine in treating patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or juvenile myelomonocytic leukemia (JMML) that has not responded to previous treatment (refractory) or that has come back after a period of improvement (recurrent). Imetelstat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as fludarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving imetelstat in combination with fludarabine and cytarabine may work better in treating patients with refractory or recurrent AML, MDS, and JMML.

开始日期2025-03-28

申办/合作机构

The Children's Oncology Group Foundation, Inc.

[+2]

NCT06576037 / Not yet recruiting临床1期IIT

Phase Ib Study of CBP-1019 in Combination With FOLFOX +/- Bevacizumab, Pembrolizumab, or Enzalutamide for Metastatic TRPV6-overexpressing Solid Tumors of Epithelial Origin

An open-label, Phase Ib dose escalation and dose expansion clinical trial evaluating the safety and efficacy of CBP-1019 combinations in patients with solid tumors of epithelial origin.

开始日期2024-12-31

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT06628310 / Not yet recruiting临床2期

A Phase 2 Randomized Study to Evaluate the Safety, Efficacy, and Optimal Dose of ABBV-400 in Combination With Fluorouracil, Leucovorin, and Budigalimab as First-Line Treatment in Subjects With Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (AndroMETa-GEA-977)

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess adverse events and change in disease activity when ABBV-400 is given in combination with Fluorouracil, Leucovorin, and a programmed cell death receptor 1 (PD1) inhibitor (Budigalimab) (AFLB) to adult participants to treat locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (mGEA).
ABBV-400 and Budigalimab are investigational drugs being developed for the treatment of mGEA. Fluorouracil and Leucovorin are drugs approved for the treatment of mGEA. This study will be divided into two stages, with the first stage treating participants with increasing doses of ABBV-400 within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. Participants will then be randomized into groups called treatment arms where one group will receive fluorouracil, leucovorin, and oxaliplatin (FOLFOX). A further two treatment groups will receive AFLB, but with two optimized doses of ABBV-400 to allow for the best dose to be studied in the future. Approximately 180 adult participants with mGEA will be enrolled in the study in 51 sites worldwide.
In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of ABBV-400 within the AFLB regimen until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive FOLFOX or receive AFLB, but with one of two optimized doses of ABBV-400The study will run for a duration of approximately 6 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

开始日期2024-12-08

申办/合作机构

AbbVie, Inc.

100 项与亚叶酸钙相关的临床结果

登录后查看更多信息

100 项与亚叶酸钙相关的转化医学

登录后查看更多信息

100 项与亚叶酸钙相关的专利（医药）

登录后查看更多信息

5,451

项与亚叶酸钙相关的文献（医药）

2024-12-15·International Journal of Cancer

A multicenter, prospective, phase II trial of second‐line aflibercept plus FOLFIRI in patients with metastatic colorectal cancer refractory to an anti‐EGFR antibody: HGCSG1801

Article

作者: Nakatsumi, Hiroshi ; Nakamura, Michio ; Sogabe, Susumu ; Takagi, Ryo ; Sagawa, Tamotsu ; Sasaki, Yusuke ; Muranaka, Tetsuhito ; Harada, Kazuaki ; Sakata, Yu ; Muto, Osamu ; Komatsu, Yoshito ; Yuki, Satoshi ; Sawada, Kentaro ; Yoshikawa, Ayumu ; Ando, Takayuki ; Dazai, Masayoshi ; Tateyama, Miki ; Kotaka, Masahito ; Hatanaka, Kazuteru ; Ishiguro, Atsushi ; Kawamoto, Yasuyuki

AbstractAflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti‐epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open‐label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin‐based chemotherapy plus an anti‐EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5‐fluorouracil [5‐FU] 400 mg/m2, and infusional 5‐FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression‐free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6‐month PFS rate was 58.8% (90% confidence interval [CI], 45.7%–72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5–11.0 months) and 18.8 months (95% CI, 12.9–26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0–36.0%) and disease control rate was 88.4% (95% CI, 74.9–96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin‐based chemotherapy plus an anti‐EGFR agent.

2024-12-01·Biochemical Pharmacology

Evaluation of UCP1162, a potent propargyl-linked inhibitor of dihydrofolate reductase with potential application to cancer and autoimmune disease

Article

作者: Nurmemmedov, Elmar ; Nelson, Craig E ; Mehta, Pratik ; Kuo, Alan ; Mosley, Adriane ; Giardina, Charles ; Ozcan Tezgin, Didem ; Krucinska, Jolanta ; Babic, Ivan ; Si, Debjani ; Wright, Dennis L. ; Wright, Dennis L ; Kurkcu, Shan ; Wright, Lee ; He, Wu

Cellular resistance can limit the effectiveness of antifolate drugs for the treatment of cancer and autoimmune diseases. Here we examine the biochemical and cellular effects of a propargyl linked, non-classical antifolate that shows exceptional potency and resilience in the background of methotrexate resistance, UCP1162. UCP1162 inhibited the human DHFR enzyme with affinity and kinetics comparable to methotrexate (MTX). UCP1162 also inhibited cancer cell proliferation and bound cellular DHFR at low nanomolar concentrations. Leucovorin suppressed the cellular effects of UCP1162, consistent with UCP1162 working as an antifolate. Like other antifolates, UCP1162 reduced acute inflammation in mice and inhibited FLS cell growth and motility. Single cell RNA-seq showed that MTX and UCP1162 generated overlapping gene expression changes after a 48-hour exposure. However, while leukemia cells (CCRF-CEM) resistant to MTX could be readily selected, UCP1162-resistant cells could not be obtained. Long-term exposure to UCP1162 resulted in static culture expressing stem cell genes (CD34, ABCG2, ABCB1), adaptive genes (TCN2, CDKN1A), and genes that might serve as therapeutic targets (TPBG/5T4, TNFRSF10A, ACE). These findings suggest that UCP1162 is a unique tool for studying cellular responses to long-term antifolate treatment and holds promise as a lead compound capable of overcoming some forms of antifolate resistance.

2024-11-14·New England Journal of Medicine

Preoperative Chemoradiotherapy for Resectable Gastric Cancer

Article

作者: Strickland, Andrew ; Mineur, Laurent ; Simes, John ; Lordick, Florian ; O'Connell, Rachel L ; Findlay, Michael ; Gebski, Val ; Leong, Trevor ; Liberman, Moishe ; Moore, Alisha ; Wong, Rebecca ; Swallow, Carol ; Michael, Michael ; Murray, William K ; Miller, Danielle ; O'Callaghan, Chris ; Zalcberg, John ; Darling, Gail ; Boussioutas, Alex ; Haustermans, Karin ; Willis, David ; Smithers, B Mark

BACKGROUNDIn Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone.METHODSWe conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life.RESULTSA total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups.CONCLUSIONSThe addition of preoperative chemoradiotherapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone among patients with resectable gastric and gastroesophageal junction adenocarcinoma. (Funded by the National Health and Medical Research Council and others; TOPGEAR ClinicalTrials.gov number, NCT01924819.).

121

项与亚叶酸钙相关的新闻（医药）

2024-11-07

·医药观澜

针对“癌症之王”，恒瑞医药公布伊立替康脂质体最新临床数据

▎药明康德内容团队报道 11月6日，恒瑞医药宣布，一项伊立替康脂质体（Ⅱ）联合5-FU/LV二线治疗经吉西他滨治疗失败后局部晚期或转移性胰腺癌的随机、双盲、平行对照、多中心3临床研究全文发表于《自然》（Nature）杂志子刊《信号转导与靶向治疗》（Signal Transduction and Targeted Therapy）。研究结果表明，伊立替康脂质体（Ⅱ）联合方案相较于对照组，胰腺癌患者死亡风险降低了37%。胰腺癌往往被称为“癌症之王”，是临床常见的消化系统恶性肿瘤，起病隐匿、恶性程度高，多数患者确诊即为晚期，复发转移率高、死亡率高，患者5年生存率（<8%）远低于其他恶性肿瘤。目前局部晚期或转移性胰腺癌的临床治疗以化疗为主，但受制于药物有限且效果不够理想，患者面临总生存期短、生活质量低等巨大挑战，特别在二线及后线治疗中，临床需求亟待满足。伊立替康作为拓扑异构酶Ⅰ抑制剂，是多个化疗方案中的基石。据恒瑞医药公开资料介绍，该公司利用脂质体技术将伊立替康包裹进磷脂双分子层中，研制出了一种可被动靶向分布于瘤体的新制剂——盐酸伊立替康脂质体（Ⅱ）。脂质体制剂的设计可保护伊立替康不会被早期转化为活性代谢物SN-38，有助于伊立替康在体循环中保持更长时间，增加药物在肿瘤内的沉积和接触，增强对肿瘤生长的抑制作用。本次在《自然》（Nature）杂志子刊发表的是胰腺癌二线治疗3期注册临床研究（PAN-HEROIC-1），旨在评估伊立替康脂质体（Ⅱ）+氟尿嘧啶（5-FU）/亚叶酸钙（LV）对比安慰剂+5-FU/LV二线治疗吉西他滨治疗失败后的转移性胰腺癌的疗效和安全性，主要研究终点为总生存（OS）期，次要研究终点包括（PFS）期、客观缓解率（ORR）等。 2018年1月至2021年5月期间，共纳入298例中国患者，按1:1随机接受伊立替康脂质体（Ⅱ）+5-FU/LV方案或安慰剂+5-FU/LV方案治疗，直至疾病进展或不耐受。OS数据分析截至2021年11月18日，中位随访时间为12.81个月。主要研究终点方面，伊立替康脂质体（Ⅱ）组较安慰剂组的中位OS期延长2.4个月（7.39个月对4.99个月），死亡风险降低了37%。次要研究终点方面，伊立替康脂质体（Ⅱ）组相对安慰剂组将PFS期显著延长了2.73个月（4.21个月对1.48个月），疾病进展或死亡风险降低64%。安全性良好。基于该3期临床研究，伊立替康脂质体（Ⅱ）已经于2023年12月获中国NMPA批准上市，联合5-FU和LV，用于既往经吉西他滨为基础的化疗治疗失败的不可切除的局部晚期或转移性胰腺癌患者的治疗。参考资料： [1]恒瑞医药伊立替康脂质体（II）联合治疗晚期胰腺癌Ⅲ期研究登上《STTT》. Retrieved Nov 6， 2024, from https://mp.weixin.qq.com/s/YkNNied9l2U0lNU5KjBCAQ 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

临床结果上市批准临床3期临床2期

2024-11-07

·普利制药300630

【首家获批】左亚叶酸钙注射液首家获国家药品监督管理局批准上市，开创普利制药国内抗肿瘤药领域新局面！

喜讯普利制药获国家药品监督管理局批准上市！ ——新品上市—— 海南普利制药股份有限公司旗下的全资子公司浙江普利药业有限公司于近日收到国家药品监督管理局（以下简称“NMPA”）所签发的的药品注册批件，视为通过一致性评价批准上市，这标志着普利制药的具备了在国内上市销售的资格，本品为国内首家获批的，将对公司拓展中国抗肿瘤药领域新市场带来深远影响。 ▲普利制药药品注册证书：2.5ml:25mg、5ml:50mg规格 ▲普利制药药品注册证书：10ml:100mg、17.5ml:175mg规格普利制药此次获批的，标志着公司国内首款抗肿瘤药物的诞生，为公司抗肿瘤药物领域的发展开创了新局面，正式开启了普利制药在抗肿瘤赛道上的征程。此次获批4个规格，分别为：2.5ml:25mg、5ml:50mg、10ml:100mg以及17.5ml:175mg，多样化规格能够更精准地满足临床用药的多样化需求，避免药物的浪费或不足，实现精准给药需求。 01 左亚叶酸钙简介左亚叶酸钙是一种叶酸类似物，与 5-氟尿嘧啶化疗药物联用可作为增效剂，用于治疗胃癌和结直肠癌；亦可作为解毒剂用于高剂量甲氨蝶呤治疗的后续治疗以减少毒性。亚叶酸钙为左旋亚叶酸钙与右旋亚叶全部药理活性成分，而右旋基本属于无活性成分。因此在与化疗药物合并使用时，左亚叶酸钙只需一半的剂量即可产生与亚叶酸钙相似的疗效，相比亚叶酸钙更为高效。最早于1995年在瑞典上市，此后陆续在葡萄牙、冰岛、丹麦、英国陆续获批上市。2011年，在美国获批上市，商品名为FUSILEV，持证商为ACROTECH BIOPHARMA INC。目前已在全球广泛上市销售。 02 左亚叶酸钙市场数据全球根据IQVIA数据，左亚叶酸钙针剂2023年全球销售额达到约1.1亿美元，其中中国市场销售占比11%，全球排名第三，中国为左亚叶酸钙主要市场之一。 ▲数据源于IQVIA数据库根据IQVIA数据，左亚叶酸钙针剂全球销量水针占比71%，粉针仅占29%，水针为全球市场的主流剂型。目前国内已上市的左亚叶酸钙均为粉针剂型，普利制药此次获批的，做为国内首款水针剂型，将使国内销售市场保持与国际同步，引领左亚叶酸钙国内销售市场由粉针转为水针的新趋势。 ▲数据源于IQVIA数据库从临床使用上来说，左亚叶酸钙水针省去了粉针复溶时间，为临床治疗节约时间，减少因稀释带来的可能污染，临床使用方便。普利制药的为中美双报产品，已于2023年5月获得美国食品药品监督管理局（FDA）的批准，除了以上已获批的美国外，普利制药的在国际上的布局也在积极进展中，其中在审批中的国家有英国，其它国家在陆续增加中。国内市场与国际市场同质量标准，同产品品质，将为国内患者提供高品质的用药选择。中国据米内网数据显示，中国国内2023年左亚叶酸钙针剂在医院销售额约为2.1亿元，同时公司的注射用亚叶酸钙国内也在申报中，预计2025年获批，届时普利制药治疗结直肠癌的市场将增加3.1亿。 ▲数据源于米内网在中国城市公立医院、县级公立医院、城市社区中心及乡镇卫生院（简称中国公立医疗机构）终端，左亚叶酸钙已成为了抗肿瘤治疗用解毒剂TOP4品种，2023年销售额超过2亿元，2024上半年再有2.44%的增长。 ▲数据源于米内网根据中华医学会发布的《2022年中国恶性肿瘤流行情况分析》显示：2022 年中国恶性肿瘤新发病例 482.47 万例，恶性肿瘤总死亡人数 257.42 万例。其中，结直肠癌新发病例 52万例，居所有恶性肿瘤第 2 位；死亡病例约 26万例，居所有恶性肿瘤第 4 位。胃癌新发病例34万例，居所有恶性肿瘤第 5位，死亡病例约 26 万例，居所有恶性肿瘤第 3 位，癌症严重威胁我国国民身体健康和生活质量。 ▲数据源于《2022年中国恶性肿瘤流行情况分析》全国结直肠癌、胃癌的发病率总体呈上升趋势，尤其是结直肠癌。2013年至2022年，结直肠癌整体发病例数由2013年34.79万例增长到2022年的51.71万例，在全国恶性肿瘤发病顺位由第四位上升为第二位。根据美国ASCO官网数据显示：结直肠癌患者的整体5年生存率为65％，且诊断为Ⅰ-Ⅲ期的生存率相对较高，一期甚至能达到94%。左亚叶酸钙为结直肠癌及胃癌常见的一线经典治疗辅助药，普利的左亚叶酸钙将为中国结直肠癌患者带来更多、更便捷的用药选择！ ▲数据源于2013-2022年《中国恶性肿瘤流行情况分析》 ▲数据源于美国ASCO官网 03 关于普利制药普利制药 1992 年成立于海口，是中国医药制剂国际化先导企业和国家工信部智能制造示范企业，已被国家工信部纳入工业转型升级中国制造 2025 年儿童药重点项目企业，2023年海南普利通过海关“AEO”高级认证。此前，海南普利及其子公司浙江普利、安徽普利也曾多次顺利通过美国FDA、欧盟EMA现场审计。作为中国医药制剂国际化先导企业，普利制药多年来一直恪守全球较高质量标准，是国内为数不多的原料药和注射剂研发和生产平台，也是为数不多的同时获得美国、中国、欧盟等药监部门批准的原料药、关键辅料、药物药剂和GMP中间体CMO/CDMO的优质供应商。安徽普利的抗肿瘤生产线车间已经通过了美国FDA的现场检查，这标志着其生产流程和产品质量符合国际标准。安徽普利抗肿瘤原料药环磷酰胺原料药也于今年获批上市，年产能可达10吨！安徽普利布局抗肿瘤领域，公司已经拥有和注射用亚叶酸钙抗肿瘤辅助药及环磷酰胺原料，同时普利制药在新质生产力方面还布局了走在国内前沿甚至国际前沿的硼中子俘获疗法、纳米药物。普利制药将继续深耕抗肿瘤领域，为全球癌症患者积极贡献普利专业力量！

上市批准免疫疗法医药出海

2024-11-06

·恒瑞医药

恒瑞医药伊立替康脂质体（II）联合治疗晚期胰腺癌Ⅲ期研究登上《STTT》

转自：中国医学论坛报今日肿瘤近日，中国药科大学附属南京天印山医院秦叔逵教授和上海交通大学医学院附属仁济医院王理伟教授共同牵头开展的一项伊立替康脂质体（Ⅱ）联合5-FU/LV二线治疗经吉西他滨治疗失败后局部晚期或转移性胰腺癌的随机、双盲、平行对照、多中心Ⅲ临床研究全文发表于《自然》（Nature）杂志子刊、国际知名医学期刊《信号转导与靶向治疗》（Signal Transduction and Targeted Therapy，IF=40.8）1。研究结果表明，伊立替康脂质体（Ⅱ）联合方案相较于对照组，胰腺癌患者死亡风险降低了37%。该研究（PAN-HEROIC-1）系中国首个取得成功的胰腺癌二线治疗Ⅲ期注册临床研究，为我国晚期胰腺癌患者二线治疗提供了新选择2。 01 研究背景胰腺癌是临床常见的消化系统恶性肿瘤，起病隐匿、恶性程度高，多数患者确诊即为晚期，复发转移率高、死亡率高，患者5年生存率（<8%）远低于其他恶性肿瘤，2022年全球胰腺癌死亡病例46.74万例，在所有恶性肿瘤中占比排第6位3。目前局部晚期或转移性胰腺癌的临床治疗以化疗为主，但受制于药物有限且效果不够理想，患者面临总生存期短、生活质量低等巨大挑战，特别在二线及后线治疗中，临床需求亟待满足。伊立替康作为拓扑异构酶Ⅰ抑制剂，是多个经典化疗方案中的基石4。尽管伊立替康已经广泛应用于临床，但普通剂型的伊立替康很难避免其药物学特性所带来的疗效降低，副作用增多的风险4，增加了临床管理难度，降低了患者的依从性。如何保护药物有效成分，提高稳定性，成为伊立替康降毒增效的关键。脂质体具有高效低毒、靶向给药等优势，已作为多种药物载体并在临床使用5,6。基于脂质体的优良载药特性，恒瑞医药历经十余年，利用脂质体专利技术将伊立替康包裹进磷脂双分子层中，研制出了一种可被动靶向分布于瘤体的新制剂——盐酸伊立替康脂质体（Ⅱ）。其具有以下特性： ①通过独有的处方设计筛选和工艺开发，获得高载药量和高包封率的伊立替康脂质体，并具有优良的稳定性7。 ②聚乙二醇化脂质体表面富集水化层，提供更好的空间阻隔，减少调理素吸附至脂质体表面，屏蔽网状内皮系统的识别和摄取，延长体内循环时间8,9。 ③通过控制脂质体的粒径<100nm，减少体内清除，延长体内滞留时间，并可更多渗透到肿瘤组织中，达到精准穿透至肿瘤部位的作用10,11。 02 研究简介基于国内胰腺癌二线治疗亟待满足的临床需求，秦叔逵教授和王理伟教授共同牵头开展的多中心，随机、双盲、对照的Ⅲ期临床研究（PAN-HEROIC-1）应运而生，旨在评估伊立替康脂质体（Ⅱ）+氟尿嘧啶（5-FU）/亚叶酸钙（LV）对比安慰剂+5-FU/LV二线治疗吉西他滨治疗失败后的转移性胰腺癌的疗效和安全性，主要研究终点为总生存（OS）期，次要研究终点包括（PFS）期、客观缓解率（ORR）等。 PAN-HEROIC-1研究设计图 2018年1月至2021年5月期间，共纳入298例中国患者，按1:1随机接受伊立替康脂质体（Ⅱ）+5-FU/LV方案或安慰剂+5-FU/LV方案治疗，直至疾病进展或不耐受。OS数据分析截至2021年11月18日，中位随访时间为12.81个月。主要研究终点方面，伊立替康脂质体（Ⅱ）组较安慰剂组的中位OS期延长2.4个月（7.39个月对4.99个月,HR 0.63，P=0.0019），死亡风险降低了37%。次要研究终点方面，伊立替康脂质体（Ⅱ）组相对安慰剂组将PFS期显著延长了2.73个月（4.21个月对1.48个月），疾病进展或死亡风险降低64%。安全性良好。 PAN-HEROIC-1研究由中国专家牵头开展，全国54家中心共同参与，入组人群均为中国患者，是基于中国国情设计的治疗方案，更贴近我国胰腺癌临床治疗实践。该研究表明伊立替康脂质体（II）联合5-FU/LV对比安慰剂联合5-FU/LV可显著延长患者总生存期（OS）1。基于此研究，恒瑞医药自主研发的盐酸伊立替康脂质体注射液（II）（商标名：越优力®）于2023年12月获批上市，联合5-FU和LV，用于既往经吉西他滨为基础的化疗治疗失败的不可切除的局部晚期或转移性胰腺癌患者的治疗。伊立替康脂质体（Ⅱ）联合方案也被纳入2024版《中国临床肿瘤学会胰腺癌诊疗指南》I级专家推荐（IA类证据）12。参考文献：1.https://doi-org.libproxy1.nus.edu.sg/10.1038/s41392-024-01948-4.2.L. Wang, S. Qin, Y. Zhou, et al. ESMO 2022: LBA61.3.WHO.Globocan 2022: Available at: https://gco.iarc.fr/today.4.Kciuk M, et al. Int J Mol Sci. 2020;21(14):4919.5.Guimarães D, et al. Int J Pharm. 2021;601:120571. 6.Bozzuto G, Molinari A. Int J Nanomedicine. 2015;10:975-999. 7.Yang W, Yang Z , Fu J , et al. Biomater Sci. 2018;7(1):419-428.8.Rommasi F,Esfandiari N.Nanoscale Res Lett. 2021;16(1):95. 9.D'souza AA, Shegokar R. Expert Opin Drug Deliv. 2016;13(9):1257-1275.10.Danaei M, et al. Pharmaceutics. 2018;10(2):57.11.Nong J, et al. Adv Drug Deliv Rev. 2022;184:114180. 12.中国临床肿瘤学会(CSCO) 胰腺癌诊疗指南2024 声明： 1.本新闻旨在分享学术前沿动态，仅供医疗卫生专业人士基于学术目的参阅，非广告用途。 2.恒瑞医药不对任何药品和/或适应症作推荐。 3.本新闻中涉及的信息仅供参考，请遵从医生或其他医疗卫生专业人士的意见或指导。医疗卫生专业人士作出的任何与治疗有关的决定应根据患者的具体情况并遵照药品说明书。排版：程梦真责编：李玉莹往期精选 | 研发创新 | 慢病创新里程碑！恒瑞首个自免创新药夫那奇珠单抗获批上市恒瑞医药新突破！中国首个自研阿片类镇痛创新药富马酸泰吉利定获批上市 | 国际化 | 海外BD再传捷报！恒瑞医药GLP-1类创新药组合实现海外许可恒瑞医药与默克达成合作，携手推进癌症创新疗法 | 重磅奖项 | 喜报！恒瑞医药荣获2023年度国家科技进步奖恒瑞医药连续六年入选全球制药企业50强榜单！ | 社会公益 | “健康中国行·重走长征路”项目启动仪式圆满举行！恒瑞提供公益支持，助力健康中国恒瑞医药集团向中国扶贫基金会捐赠3000万设立“健康帮扶基金”

临床3期临床结果临床成功免疫疗法

100 项与亚叶酸钙相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D01211	亚叶酸钙	V03AF03	DB00650

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
结直肠癌	日本	Pfizer Japan, Inc.	2003-07-17
结直肠癌	日本	Taiho Pharmaceutical Co., Ltd.	2003-07-17
贫血	中国	山西振东泰盛制药有限公司	1996-01-01
药物中毒	日本	Pfizer Japan, Inc.	1963-01-11

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
III期结肠癌	临床2期	意大利	Pfizer Inc.	2001-01-01
III期结肠癌	临床2期	奥地利	Pfizer Inc.	2001-01-01
III期结肠癌	临床2期	比利时	Pfizer Inc.	2001-01-01
III期结肠癌	临床2期	西班牙	Pfizer Inc.	2001-01-01
III期结肠癌	临床2期	法国	Pfizer Inc.	2001-01-01
III期结肠癌	临床2期	德国	Pfizer Inc.	2001-01-01
III期结肠癌	临床2期	瑞士	Pfizer Inc.	2001-01-01
III期结肠癌	临床2期	英国	Pfizer Inc.	2001-01-01
转移性结直肠癌	临床2期	美国	Pfizer Inc.	1999-11-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03483038 (NEO-Nal-IRI, CTgov)	临床2期	胰腺腺癌	45	LEUCOVORIN CALCIUM+Liposomal Irinotecan+Oxaliplatin+Fluorouracil	鬱鏇廠願膚鑰齋窪構膚(繭淵窪網觸鏇鬱艱願築) = 選艱憲願憲廠觸艱範繭繭簾鏇網窪窪蓋膚鏇觸 (醖艱壓艱襯獵願憲獵簾, 製蓋醖鏇糧淵膚顧鏇蓋 ~ 範餘壓衊鑰範觸壓窪範) 更多	-	2024-09-23
NCT05026905 (TCOG T5221, ESMO2024) 人工标引	临床2期	胰腺癌一线	50	GASL (Gemcitabine plus nab-paclitaxel and S-1/leucovorin)	(襯鏇糧選鬱壓鹹鏇壓醖) = 觸積獵願觸膚鏇鬱鹹獵艱顧顧選構觸廠鏇製獵 (齋淵糧簾鬱衊構齋齋簾 ) 更多	积极	2024-09-16
				GAP (Gemcitabine plus nab-paclitaxel and oxaliplatin)	(襯鏇糧選鬱壓鹹鏇壓醖) = 襯壓願鏇膚網壓齋網獵艱顧顧選構觸廠鏇製獵 (齋淵糧簾鬱衊構齋齋簾 ) 更多
NCT03586869 (QUILT-3.080, CTgov)	临床1/2期	胰腺癌	3	Avelumab+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+ETBX-011+fluorouracil+ALT-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+haNK for infusion+Leucovorin+GI-6207+bevacizumab+Oxaliplatin+Capecitabine	積襯糧鏇襯觸積獵繭窪(艱壓積衊艱齋製願鬱壓) = 積憲夢襯範餘觸網艱淵壓窪蓋艱齋築鑰壓鑰艱 (觸衊蓋壓繭壓廠夢鏇願, 壓願繭廠窪築廠鑰積獵 ~ 膚網製鏇憲選齋齋襯簾) 更多	-	2024-08-27
NCT01595321 (CTgov)	临床2期	胰腺腺癌	19	Stereotactic Body Radiation+Leucovorin Calcium+irinotecan+oxaliplatin+Irinotecan hydrochloride+FLUOROURACIL (Cohort 1: SBRT and FOLFIRINOX)	淵築繭觸糧憲蓋選製淵(顧蓋簾膚構醖鬱構構夢) = 鬱憲獵觸齋醖製蓋窪鬱獵淵繭顧夢鏇醖鏇廠願 (夢選築簾壓構願膚蓋夢, 糧襯夢觸顧夢窪齋齋壓 ~ 淵鏇衊齋繭簾餘顧糧餘) 更多	-	2024-08-14
				Stereotactic Body Radiation (Cohort 2: SBRT and Modified FOLFIRINOX)	淵築繭觸糧憲蓋選製淵(顧蓋簾膚構醖鬱構構夢) = 壓簾鑰範夢願襯鬱夢積獵淵繭顧夢鏇醖鏇廠願 (夢選築簾壓構願膚蓋夢, 築醖壓襯齋網顧憲蓋範 ~ 繭顧壓憲餘選夢憲網齋) 更多
NCT03387085 (QUILT-3.067, CTgov)	临床1/2期	三阴性乳腺癌	9	SBRT+Aldoxorubicin HCl+GI-6301+GI-4000+ETBX-061+ETBX-051+ETBX-011+5-fluorouracil+N-803+nab-paclitaxel+CYCLOPHOSPHAMIDE+Avelumab+haNK for Infusion+Leucovorin+GI-6207+Cisplatin+Bevacizumab+Capecitabine	製淵窪蓋製製願艱襯鑰(鬱壓艱艱鹽窪廠遞網範) = 範觸艱顧餘醖廠積築製顧獵範淵齋製膚鹽廠憲 (範醖鏇構鑰顧糧夢遞築, 鏇淵壓襯網觸繭膚鹽鏇 ~ 構膚製獵繭願醖糧觸艱) 更多	-	2024-08-09
NCT03387111 (CTgov)	临床1/2期	鳞状细胞癌	4	SBRT+Aldoxorubicin HCl+GI-6301+GI-4000+cetuximab+ETBX-061+ETBX-051+ETBX-011+Necitumumab+fluorouracil+N-803+ETBX-021+nab-paclitaxel+Cyclophosphamide+Avelumab+haNK for infusion+Leucovorin+GI-6207+Cisplatin+Bevacizumab+Capecitabine	衊積觸繭齋衊憲遞鏇構(蓋選獵鬱築窪願蓋遞艱) = 選夢夢鏇膚範網艱獵製繭膚餘顧夢鬱齋觸衊構 (憲遞鹹鑰鹹網簾齋構襯, 鏇艱蓋簾觸選膚獵鹽醖 ~ 顧構鏇壓獵淵鹽遞廠廠) 更多	-	2024-08-05
NCT03336216 (CTgov)	临床2期	晚期胰腺腺癌	205	nab-paclitaxel+Leucovorin+gemcitabine+Irinotecan+5-Fluorouracil (Arm A: Investigator Choice)	衊餘簾顧觸醖積觸壓構(製積獵獵窪願鬱鏇鏇願) = 膚醖壓艱壓鏇壓鹹廠窪夢糧鏇窪鏇觸窪積構鹹 (獵遞衊窪願網齋網鹽顧, 鏇築糧淵窪淵積窪齋觸 ~ 顧網遞醖壓遞襯築鏇壓) 更多	-	2024-07-23
				Cabiralizumab+Nivolumab (Arm B: Cabiralizumab + Nivolumab)	衊餘簾顧觸醖積觸壓構(製積獵獵窪願鬱鏇鏇願) = 膚鏇鏇顧顧遞襯鬱鑰壓夢糧鏇窪鏇觸窪積構鹹 (獵遞衊窪願網齋網鹽顧, 憲鏇網糧襯廠製壓襯艱 ~ 醖襯鑰築衊齋願遞糧鏇) 更多
NCT05546411 (CTgov)	临床2期	胰腺腺癌	8	Chemoradiation+NIS793+Leucovorin+irinotecan+Irinotecan+oxaliplatin+FLUOROURACIL (mFOLFIRINOX + NIS793)	築衊鹽繭積鏇淵繭膚窪(襯鹹齋膚窪醖窪簾築夢) = 範鑰淵範簾鹹衊襯簾鹹糧憲醖製鑰鏇簾顧鏇範 (築糧衊構壓艱遞齋壓遞, 壓願鏇蓋膚簾製觸鏇鏇 ~ 淵製製衊鑰蓋顧選夢築) 更多	-	2024-07-16
				Chemoradiation+Leucovorin+irinotecan+Irinotecan+oxaliplatin+FLUOROURACIL (mFOLFIRINOX)	築衊鹽繭積鏇淵繭膚窪(襯鹹齋膚窪醖窪簾築夢) = 積獵廠積鏇淵簾願醖窪糧憲醖製鑰鏇簾顧鏇範 (築糧衊構壓艱遞齋壓遞, 鹹糧遞衊獵選簾選糧顧 ~ 遞夢構選築鑰憲構願繭) 更多
NCT02352337 (PRODIGE 35-PANOPTIMOX \| PANOPTIMOX, CTgov)	临床2期	胰腺继发性恶性肿瘤	276	Leucovorin Calcium+irinotecan+oxaliplatin+Irinotecan hydrochloride+FLUOROURACIL (FOLFIRINOX)	鹹獵壓淵蓋夢淵鹽願齋(壓築網選簾醖鬱構鬱築) = 餘獵顧憲鹽窪窪積淵築廠遞顧選顧壓製廠糧淵 (製淵簾衊簾製廠艱鬱鏇, 艱積鹹糧積衊壓憲夢製 ~ 醖積願簾顧願鏇齋夢獵) 更多	-	2024-07-10
				LV+irinotecan+oxaliplatin+Irinotecan hydrochloride+FLUOROURACIL (FOLFIRINOX + LV5FU2 in Maintenance)	鹹獵壓淵蓋夢淵鹽願齋(壓築網選簾醖鬱構鬱築) = 醖選願醖積鏇醖蓋醖構廠遞顧選顧壓製廠糧淵 (製淵簾衊簾製廠艱鬱鏇, 窪蓋夢膚鹹鏇夢鏇選憲 ~ 憲鏇獵壓齋構壓顧製齋) 更多
NCT03750786 (AGENT, ESMO_GI2024) 人工标引	临床3期	转移性结直肠癌一线	59	Arfolitixorin combination with 5-FU, oxaliplatin, and bevacizumab. (the Greek patient subpopulation)	(醖齋餘鹽繭鹽觸觸鹹簾) = 觸鏇鬱獵鬱獵遞蓋願製糧鹹積醖艱繭壓選鹽繭 (築衊鑰構壓廠醖衊積齋, 22.1 ~ 63.4) 更多	-	2024-06-29
				Leucovorin combination with 5-FU, oxaliplatin, and bevacizumab. (the Greek patient subpopulation)	(醖齋餘鹽繭鹽觸觸鹹簾) = 衊鑰艱選艱網壓窪繭壓糧鹹積醖艱繭壓選鹽繭 (築衊鑰構壓廠醖衊積齋, 21.5 ~ 55.1) 更多