Phase 1 Trial of Nab-Paclitaxel PIPAC (Pressurized Intraperitoneal Aerosolized Chemotherapy) Given in Combination With Second-Line Therapy for Gastric Cancer With Peritoneal Metastases

This phase I trial tests the safety, side effects and best dose of nab-paclitaxel pressurized intraperitoneal aerosolized chemotherapy (PIPAC) in combination with second-line chemotherapy, paclitaxel and ramucirumab, and tests how well they work in treating stomach cancer that has spread from where it first started to the tissue that lines the abdominal wall and organs (peritoneal metastases). Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. PIPAC delivers chemotherapy, such as nab-paclitaxel, that has been turned into a fine mist (aerosolized) at a high pressure directly into the abdominal cavity. Aerosolized chemotherapy delivered directly into the peritoneal space has been shown to deliver higher drug concentrations to the tumor. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving nab-paclitaxel PIPAC in combination with paclitaxel and ramucirumab may be safe, tolerable, and/or effective in treating gastric cancer patients with peritoneal metastases.

开始日期2025-10-17

申办/合作机构

City of Hope National Medical Center

[+1]

NCT05411237

/ Not yet recruiting临床3期IIT

A Phase III, Randomized, Open-Label, Non-Inferiority Study of Paclitaxel and Pegylated Liposomal Doxorubicin for Treatment of HIV-related Kaposi Sarcoma in Resource-Limited Settings

This study is being done to determine if two different anti-cancer drugs, paclitaxel (PTX) and pegylated liposomal doxorubicin (PLD) have similar effects on treating Kaposi Sarcoma (KS) in people living with HIV (human immunodeficiency virus) in sub-Saharan Africa. Patients with HIV-related KS will receive either PTX or PLD once every 3 weeks for a total of six cycles.

开始日期2025-09-15

申办/合作机构

National Cancer Institute

NCT06795009

/ Not yet recruiting临床1期IIT

Phase I/IB Study of Zanzalintinib in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer

The purpose of this study is to determine the recommended Phase 2 dose of zanzalintinib when given in combination with paclitaxel in patients with recurrent high-grade uterine cancer. Other objectives include overall safety and tolerability as well as rates of response.

开始日期2025-05-31

申办/合作机构

Washington University School of Medicine

[+2]

100 项与紫杉醇相关的临床结果

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100 项与紫杉醇相关的转化医学

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100 项与紫杉醇相关的专利（医药）

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67,688

项与紫杉醇相关的文献（医药）

2025-12-31·JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Selisistat, a SIRT1 inhibitor, enhances paclitaxel activity in luminal and triple-negative breast cancer: in silico, in vitro, and in vivo studies

Article

作者: Bartuzi, Damian ; Stepulak, Andrzej ; Kalafut, Joanna ; Okon, Estera ; Wawruszak, Anna ; Czerwonka, Arkadiusz ; Luszczki, Jarogniew

Sirtuins (SIRTs) are NAD+-dependent histone deacetylases, which play a key role in cancer progression; however, their prognostic values in breast cancer (BC) remain a subject of debate and controversy. Accumulative evidence suggests that each sirtuin possesses individual character, implicating its role in the regulation of multifaceted biological functions leading to BC initiation, progression and metastasis. Selisistat (EX527) is a potent, cell permeable, highly selective SIRT1 inhibitor. In the study, the tumour-suppressive effects of the SIRT1 inhibitor EX527 (selisistat) alone and in combination with paclitaxel (PAX) in different breast cancer cell lines and zebrafish xenograft models were investigated. The type of pharmacological drug-drug interaction between EX527 and PAX was determined using the isobolographic method. EX527 and PAX used individually inhibited proliferation, induced apoptosis and caused cell cycle arrest in G1 and subG1/G2 phases. Interestingly, the combination of these compounds used in the 1:1 dose-ratio augmented all these effects (IC_50add 29.52 ± 3.29 - 38.45 ± 5.26). The co-treatment of EX527 with PAX generated desirable additive drug-drug interaction. The simultaneous application of EX527 and PAX induced a stronger inhibition of tumour growth compared to individual treatments in zebrafish xenografts. In silico analysis revealed a protein-protein interaction pathway (SIRT1-AKT-S1PR1-GNAI1/GNAO1-Tubulin) connecting molecular targets of both ligands. To summarise, the combination of EX527 and PAX more effectively impairs breast cancer cell growth compared to individual treatments. However, further investigations are required to clarify the specific targets and molecular mechanisms underlying the activity of EX527:PAX in other preclinical models.

2025-12-31·CANCER BIOLOGY & THERAPY

Sulfatase 2 inhibition sensitizes triple-negative breast cancer cells to paclitaxel through augmentation of extracellular ATP

Article

作者: Schnell, Patrick M. ; Zhang, Xiaoli ; Datta, Jharna ; Rubinstein, Mark P. ; Manouchehri, Jasmine M. ; Marcho, Lynn M. ; Ganju, Ramesh K. ; Mittra, Arjun ; Yue, Yu ; Carson, William E. ; Stover, Daniel ; Cherian, Mathew A. ; Ramaswamy, Bhuvaneswari

The highest incidence and cancer-related mortality rate among women worldwide is due to breast cancer. Triple-negative breast cancers (TNBC) are associated with more inferior outcomes than other breast cancers because of their progressive nature and the deficit in available therapies. Therefore, there is a need for new therapeutic approaches. Our lab determined that chemotherapy induces the release of extracellular adenosine triphosphate (eATP), and, hence, augments TNBC cells' response to chemotherapy. Despite this, eATP concentrations are restricted by a variety of extracellular ATPases. We propose that, as an ATPase inhibitor, heparan sulfate (HS) would augment eATP concentrations and TNBC vulnerability induced by chemotherapy. Sulfatase 2 (SULF2) removes sulfate from HS, the functional group essential for ATPase inhibition. Consequently, we propose that TNBC cell death and eATP release induced by chemotherapy would be intensified by SULF2 inhibitors. We examined eATP and cell viability in paclitaxel-treated TNBC and nontumorigenic immortal mammary epithelial MCF-10A cells in the presence of OKN-007, a selective SULF2 inhibitor, and/or heparan sodium sulfate. Furthermore, sulfatase 1 (SULF1) and SULF2 protein expressions were ascertained. We found that the expression of SULF2 was greater in TNBC cell lines when compared to MCF-10A cells. The release of eATP and loss of TNBC cell viability induced by chemotherapy was enhanced by OKN-007. The co-treatment of chemotherapy and OKN-007 also attenuated cancer-initiating cells. This data implies that the combination of SULF2 inhibitors with chemotherapy augments eATP and decreases cell viability of TNBC greater than chemotherapy alone.

2025-12-31·JOURNAL OF MEDICAL ECONOMICS

Cost-efficiency and expanded access modeling of conversion to biosimilar bevacizumab in metastatic colorectal and non-squamous non-small cell lung cancer in Medicare

Article

作者: Bernauer, Mark ; Roth, Joshua A. ; Dorman, Stephanie ; Kratochvil, David

BACKGROUND:

Biosimilars to originator bevacizumab (Avastin), such as bevacizumab-bvzr (Zirabev), can deliver substantial savings and/or expanded access to biologic therapy for patients with metastatic colorectal (mCRC) and non-squamous non-small cell lung cancer (mNSCLC). The objective of this study is to explore the cost-efficiency and budget-neutral expanded access of bevacizumab-bvzr in mCRC and mNSCLC in Medicare.

METHODS:

We developed a Medicare payer perspective simulation model of patients treated for mCRC and mNSCLC to estimate cost-savings from converting bevacizumab (originator) to bevacizumab-bvzr or alternative biosimilars such as bevacizumab-awwb, -maly, and -abcd. The target patient population receiving annual first-line systemic therapy was calculated using Medicare enrollment data, SEER cancer incidence rates in patients age ≥65, and an assumption that 39.3% and 77.2% of new diagnoses receive systemic therapy for mCRC and mNSCLC respectively based on recent evidence. 76.0% of systemically treated mCRC patients and 11.4% of incident mNSCLC patients were expected to be treated with bevacizumab-based regimens based on recent evidence. Costs were derived from the 2024 Average Sales Price (ASP). Results include per-patient per-month (PPPM) cost savings (vs. originator), total monthly savings in the cohort, and number needed to convert (NNC) to biosimilar to fund the treatment of an additional 100 patients.

RESULTS:

PPPM savings from conversion to bevacizumab-bvzr were $4,205 in mCRC and $8,410 in mNSCLC. In 100% conversion scenarios, full cohort monthly savings were $27,664,432 in mCRC (n = 6,579) and $32,319,323 in mNSCLC (n = 3,843), respectively. At 100% conversion, monthly savings from biosimilar conversion could fund up to 13,887 additional mCRC patient-months of treatment with bevacizumab-bvzr + FOLFOX, and up to 8,959 additional mNSCLC patient-months of treatment with bevacizumab-bvzr + paclitaxel + carboplatin. In mCRC and mNSCLC the biosimilar NNC from the originator was 47 and 43, respectively. The biosimilar NNC from other biosimilars ranged from 60-4,564 and 55-4,422 for mCRC and NSCLC, respectively.

CONCLUSION:

In the first cost-efficiency and expanded access study of biosimilar bevacizumab in mCRC and mNSCLC, we find that bevacizumab-bvzr-based regimens can result in substantial cost savings relative to originator-based first line treatment in Medicare. These cost savings could be reinvested to treat a substantial number of additional patients with mCRC or mNSCLC, or fund other costs of care in Medicare, on a budget-neutral basis.

2,858

项与紫杉醇相关的新闻（医药）

6 小时之前

·小药说药

FGFR靶向治疗的临床进展

-01-引言成纤维细胞生长因子（FGF）通过FGF受体（FGFR1-4）发出信号，协调胎儿发育，有助于组织和全身稳态，但FGFR基因的融合、重排或突变也可能促进肿瘤发生。FGFR融合可分为I型（非受体型，由融合伴侣的N端置换引起，如BCR-FGFR1和ZYM2-FGFR1）、IIa型（受体型，也由融合伴侣N端置换产生；如FN1-FGFR1、KLK2-FGFR2）或IIb型（受体型，由融合伴侣C端置换产生；如FGFR2-BICC1、FGFR3-TACC3）。在实体瘤中检测到的FGFR变化包括非小细胞肺癌中的FGFR1扩增（20%）、乳腺癌中的FGFR 1/2扩增（7-23%）、尿路上皮癌中的FGFR3突变（10-60%）或FGFR3融合（6%）、肝内胆管癌中的FGFR2融合（10-20%）、子宫内膜癌中的FGFR2突变（12%）和胃癌中FGFR2的扩增（5-10%）。在约7.0%的未经选择的癌症患者中可以检测到FGFR基因的改变。目前，已经开发出了多种FGFR靶向药物，包括泛FGFR抑制剂（erdafitinib和futibatinib）、FGFR1/2/3抑制剂（infigratinib和pemigatinib），以及一系列更具特异性的药物，其中一些已进入临床使用。Erdafitinib已被批准用于携带FGFR2/3突变的尿路上皮癌患者，futibatinib和pemigatinib被批准治疗携带FGFR2融合或重排的胆管癌患者。这些药物的临床益处在一定程度上受到高磷血症的限制，这是由于FGFR1的脱靶抑制以及FGFR基因中耐药性突变的出现。下一代小分子抑制剂，如lirafugratinib和LOXO-435，以及FGFR2特异性抗体bemarituzumab，有望降低高磷血症的风险，并有能力克服某些耐药性突变。-02-一、FGFR的结构和信号通路FGFs由具有球状或非典型β三叶结构的保守核心结构域组成，可分为典型FGFs（FGF1-10、FGF16-18、FGF20和FGF22）、内分泌型FGF（FGF19/FGF15、FGF21和FGF23）以及FGF同源因子（FGF11-14）。全长FGF受体（FGFR1-4）是I型跨膜蛋白，具有三个细胞外免疫球蛋白样结构域和一个胞内酪氨酸激酶结构域。典型的FGF与硫酸乙酰肝素辅因子一起通过FGFR传递信号，而内分泌型FGF与klotho共受体（KLA和KLB）和硫酸乙酰肝素辅助因子一起通过FGFR传递信号。FGF–FGFR信号传导参与细胞存活、增殖、代谢、迁移和分化，包括生理作用，如协调胎儿发育和维持组织和/或全身稳态。这些受体也可以驱动肿瘤的发展。FGFR中配体依赖性二聚化或病理改变通过自身抑制机制释放而导致内源性激酶激活。FGFR激活导致FRS2依赖性激活PI3K–AKT、RAS–ERK和磷脂酶Cγ（PLCγ）依赖性二酰基甘油（DAG）–PKC和IP3–Ca2+信号。癌症患者的FGFR改变通过异常的FGFR信号传导促进肿瘤发生：FGFR扩增导致FGFR过度表达和下游信号通路过度激活；FGFR融合或重排导致融合伴侣介导的FGFR二聚化、磷酸化改变和异常的下游信号传导；细胞外区或跨膜结构域中的FGFR突变通过改变对FGF配体的特异性或亲和力，以及配体非依赖性二聚化来激活FGFR；酪氨酸激酶结构域中的FGFR突变由于自身抑制机制的破坏而结构性性地激活FGFR。-03- 二、小分子FGFR抑制剂几种小分子FGFR抑制剂已被开发用于治疗具有FGFR改变的癌症患者，如尿路上皮癌、乳腺癌、胃癌、肝癌、肺癌、卵巢癌和宫颈癌。能够与酪氨酸激酶结构域的ATP结合位点结合的FGFR抑制剂通常分为多激酶FGFR抑制剂或选择性FGFR抑制剂。Derazatinib、dovitinib、tasurgratinib、lenvatinib、lucitanib、nintedanib和ponatinib都是多激酶FGFR抑制剂，对FGFR以外的多种RTK具有活性。然而，由于其广泛的活性，与选择性FGFR抑制剂相比，多激酶FGFR抑制剂的作用机制和不良反应都很复杂。选择性FGFR抑制剂包括泛FGFR、FGFR1/2/3和FGFR2/3抑制剂以及选择性FGFR2、FGFR3或FGFR4抑制剂。泛FGFR抑制剂包括 erdafitinib, futibatinib, rogaratinib和resigratinib；FGFR1/2/3抑制剂包括pemigatinib, infigratinib, fexagratinib和zoligratinib；Lirafugratinib是一种选择性FGFR2抑制剂，LOXO-435是一种选择FGFR3抑制剂，roblitinib和fissotioninib是选择性FGFR4抑制剂。目前，根据在II期试验中观察到的疗效和耐受性，美国食品药品监督管理局（FDA）在这些适应症的二线或更后线的治疗中加速批准erdafitinib、futibatinib、infigratinib和pemiginib。在erdafitinib的临床研究（BLC2001）中，根据FGFR3或FGFR2/FGFR3融合物中至少一种突变的存在，选择局部晚期和/或不可切除的尿路上皮癌患者。整体队列的ORR为40%，中位无进展生存期（mPFS）和中位总生存期（mOS）分别为5.5个月和13.8个月。46%的患者出现≥3级不良事件，在初步分析中包括低钠血症（11%）、口腔炎（10%）和乏力（7%），以及长期随访的指甲（15%）、口炎（14%）和皮肤事件（8%）。在FIGHT-203的II期研究中，在携带I型FGFR1融合（如ZMYM2–FGFR1或BCR–FGFR2）的MLN患者中测试了pemiginib的药效和安全性。其中77%（24/31）的患者对pemiginib有完全响应。常见的≥3级不良事件包括贫血（18%）、口腔炎和四肢疼痛（均为12%）。2022年8月，FDA批准了pemiginib用于携带FGFR1融合的复发性和/或难治性MLN患者。任何级别的高磷血症都发生在大多数接受泛FGFR抑制剂或FGFR1/2/3抑制剂的患者中。这种不良反应很可能反映了泛FGFR或FGFR1/2/3抑制剂对FGF23信号传导的抑制，因为这种分泌蛋白依赖于与近端小管上皮细胞膜上的FGFR1和klotho的结合。该复合物通过抑制磷酸钠协同转运蛋白（NPT2a/c）调节肾脏中的磷酸盐吸收。FGFR1在这一过程中的作用得到证实，因此，开发FGFR2特异性和FGFR3特异性抑制剂有望避免或降低这种不良反应的发生率。-04-三、FGFR抑制性单克隆抗体在靶向FGF/FGFR信号的生物制剂中，bemarituzumab是目前正在III期试验中评估的唯一药物。bemarituzumab是一种人源化抗FGFR2b抗体，其抑制FGF7、FGF10和FGF22的结合，从而抑制癌细胞中配体诱导的FGFR2b信号传导，并且由于修饰的Fc结构域对自然杀伤细胞上的人FcγRIIIA受体的亲和力增加，因此具有诱导抗体依赖性细胞介导的细胞毒性（ADCC）的能力。在一项涉及晚期FGFR2b过表达胃和胃食管交界腺癌（GEA）患者的I期试验中，bemarituzumab单药治疗显示出可接受的耐受性，ORR为18%（5/28）。随后，在携带FGFR2扩增或FGFR2过表达的GEA患者的II期FIGHT试验中，将bemarituzumab与mFOLFOX6（包括氟嘧啶、亚叶酸和奥沙利铂）联合测试。bemarituzumab联合化疗组和安慰剂联合化疗组患者的ORR分别为53%和40%，mPFS分别为9.5个月和7.4个月（P=0.073)。bemarituzumab的其他几项试验，包括评估bemarituzumab联合mFOLFOX6加(NCT0511626) 或不加(NCT050252801) nivolumab在先前未经治疗的晚期GEA患者中的研究正在进行中。-05-四、新型FGFR靶向疗法蛋白水解靶向嵌合体（PROTAC）、嵌合抗原受体（CAR）T细胞、抗体偶联药物（ADC）、放射免疫偶联物（RICs）和可溶性受体是能够靶向FGF–FGFR信号级联的潜在新治疗模式，其中一些已经或正在临床试验中进行测试。PROTACPROTAC具有双重部分，使其能够与靶蛋白和E3泛素连接酶相互作用，从而诱导靶蛋白的泛素化介导的蛋白酶体降解。LC-MB12是一种基于infigratinib的PROTAC，能够优先降解FGFR2，并抑制表达TEL–FGFR2融合的Ba/F3细胞和FGFR2扩增的SNU16癌细胞的增殖。相比之下，DGY-09-192是另一种基于 infigratinib的PROTAC，旨在募集von Hippel–Lindau蛋白（VHL），从而优先降解FGFR1和FGFR2。这些药物目前仍处于临床前开发阶段。CAR-T细胞由于PAX3–FOXO1的下游作用，FGFR4在儿科横纹肌肉瘤中普遍过表达。然而，N535K和V550L等耐药性突变通常在治疗前出现，这可能会限制小分子抑制剂的有效性。因此，研究人员开发了靶向FGFR4的CAR-T细胞，如RJ154-HL和3A11，具有不同的靶向FGFR4的scFv。目前，靶向FGFR的CAR-T细胞也仍处于临床前开发阶段。基于抗体的药物Aprutumab是一种全人源抗FGFR2抗体，它识别FGFR2b和FGFR2c亚型共同N末端区域P23、L27和E29周围的表位，并已被证明能诱导这些变体的内化和运输至溶酶体降解。Aprutumab和bemarituzumab在I期临床试验中均显示出良好的安全性和耐受性。目前，bemarituzumab已作为联合疗法进行II期和III期临床试验，而Aprutumab用于开发ADCs和RICs。Aprutumab ixadotin（前身为BAY-1187982）是具有不可裂解连接子的抗FGFR2 ADC，LY3076226是具有可裂解连接子的抗FGFR3 ADC。然而，测试这两种药物的第一阶段试验(nct22368951)由于耐受性差和活性有限而终止。此外，Aprutumab和抗FGFR3抗体vofatamab分别用于FGFR2靶向的RIC（227Th-Aprutumab，BAY 2304058）和FGFR3靶向的RIC，225Ac-vofatamab（FPI-1966）和111In vofatamab（FPI-1967）。BAY 2304058仍处于临床前开发阶段，而FPI-1966（用于放射免疫疗法）和FPI-1967（用于放射成像）目前正在I/II期试验(NCT05363605)中进行测试，用于表达FGFR3的晚期实体瘤患者。可溶性FGFR受体可溶性FGFR受体，如衍生自FGFR1c的细胞外结构域的FP-1039和衍生自FGFR 3c的细胞外区域的Recifecept，是另一类通过充当诱饵受体来捕获FGFR配体的重组蛋白药物。FP-1039已显示对促有丝分裂FGF配体具有高亲和力，并且在FGFR1扩增的肺癌和FGFR2突变的子宫内膜癌的小鼠异种移植模型中具有抗肿瘤作用。FP-1039在一期试验中具有可接受的耐受性。测试FP-1039与各种化疗联合用药的Ib期试验(NCT01868022) 显示同时接受紫杉醇和卡铂治疗的鳞状非小细胞肺癌患者的ORR为47%，同时接受培美曲塞和顺铂治疗的恶性胸膜间皮瘤患者的ORR为39%。-06-结语目前，小分子FGFR抑制剂和FGFR靶向抗体药物已在临床后期试验中进行开发和测试，其中几种小分子FGFR抑制剂已被批准用于FGFR改变的癌症患者。尽管如此，某些不良事件，如FGFR1脱靶抑制引起的高磷血症和获得性耐药性，仍然限制了这些药物的临床益处。选择性第三代抑制剂，如特异性靶向FGFR2或FGFR3的抑制剂，正在临床开发中，这些药物可能避免或显著降低高磷血症的风险，并可能克服突变介导的耐药性。参考资料：1.FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions. Nat Rev Clin Oncol.2024 Feb 29公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

引进/卖出临床结果临床2期

17 小时之前

·ioncology

国际大咖Dr. Girard点评：SOHO-01和COCOON研究对肺癌治疗的启示

点上方蓝字“ioncology”关注我们，然后点右上角“…”菜单，选择“设为星标”ELCC 2025 微专辑扫描二维码可查看更多内容在2025年欧洲肺癌大会（ELCC）上，巴黎居里研究所肿瘤内科主任Nicolas Girard教授重磅发布SOHO-01和COCOON试验数据，并作题为"胸腺上皮肿瘤全身治疗最新进展"的专题报告。应《肿瘤瞭望》邀请，Girard教授对SOHO-01和COCOON研究结果以及胸腺上皮肿瘤治疗进展进行了深度解读。您在2025 ELCC报告了I/II期SOHO-01研究的两个扩展队列的结果（摘要3O）。请谈谈BAY 2927088对既往接受过治疗HER2突变型非小细胞肺癌（NSCLC）患者的安全性和有效性。Dr. Girard：HER2突变型NSCLC是NSCLC的一小部分，占2-4%。BAY 2927088是一种口服酪氨酸激酶抑制剂，可以抑制HER2。SOHO-01研究评估了BAY 2927088在HER2突变型NSCLC患者中的疗效。在剂量扩展阶段采用每日两次，每次20 mg的剂量。我在2025年ELCC大会上展示了两组患者的研究结果。第一组患者是未接受过HER2靶向治疗但之前接受过全身治疗的患者（n=44）；第二组患者是之前接受过HER2靶向抗体药物偶联物（ADC）治疗的患者（n=34）。第一组患者中，研究者评估的客观缓解率（ORR）高达70.5%，疾病控制率（DCR）为81.8%，中位缓解持续时间（DOR）长达8.7个月，意味着患者在接受化疗±免疫治疗后，BAY 2927088疗法仍具有很高的疗效。第二组患者中（超过一半的患者之前接受过≥三线治疗），ORR为35.3%，DCR为52.9%，中位DOR为9.5个月，在接受化疗、免疫检查点抑制剂和ADC治疗后别无选择的情况下，这个数字相当高。BAY 2927088的安全性主要体现在腹泻（1/2级），目前没有患者因腹泻而停药。腹泻是最常见的副作用，我们可能需要对腹泻进行预防性治疗。我们正在进行一项III期临床试验SOHO-02，该试验旨在对比HER2突变型NSCLC患者接受一线BAY 2927088和化疗+免疫治疗。（上下滑动可查看）Dr. Girard: I am Nicolas Girard. I am Head of Medical Oncology at Institut Curie in Paris.HER2 NSCLC is a small subset of NSCLC, 2-4%. We have BAY 2927088 (BAY 88), which is an oral tyrosine kinase inhibitor that is inhibiting HER2. The SOHO-01 study assessed this compound in patients with EGFR HER2-mutated NSCLC. After dose expansions, dosing of 20mg twice daily was chosen for expansion. At ELCC 2025, I presented the results of two cohorts. The first one being a cohort of patients who were HER2-targeted therapy naïve, but who had previously received systemic therapy, The second was patients who had received prior treatment with HER2-targeting antibody-drug conjugates. Forty-four patients and 34 patients were treated respectively. What we see from the SOHO-01 trial is a high response rate in HER2-targeted treatment naïve patients – 72%, which is quite high. There was a duration of efficacy of 9 months in this cohort of patients is quite long. It means that after treatment with chemotherapy plus or minus immunotherapy, BAY 88 has a high efficacy. The second cohort were previously treated patients with three or more lines of therapy in more than half the patients. We see a response rate of 35% and a control rate of 53%. This is quite high in the setting of having no more option after treatment with chemotherapy, IO and ADCs. The safety of BAY 88 was mostly diarrhea (grade 1/2), with no discontinuation due to diarrhea. We probably need to implement prophylactic management for diarrhea, which was the most frequent side effect. We have an ongoing phase III trial, SOHO-02, in the first-line setting, versus chemotherapy and immunotherapy for patients with EGFR-mutated NSCLC.根据您在2025 ELCC汇报的COCOON试验结果（摘要10MO），对于接受埃万妥单抗联合兰泽替尼治疗的EGFR突变型晚期NSCLC患者，如何预防中度至重度皮肤不良事件？Dr. Girard：COCOON试验的主要目的是评估预防性治疗能否降低EGFR突变型局部晚期/转移性NSCLC患者接受埃万妥单抗+兰泽替尼治疗前12周出现的≥2级皮肤病副作用。EGFR突变NSCLC的标准治疗方案是奥希替尼，在中国和亚洲还有其他第三代TKI可选。随着MARIPOSA研究证明埃万妥单抗联合兰泽替尼相比奥希替尼显著改善总生存期（两组中位总生存差异超过1年），该疗法将成为此类患者一线治疗的新标准。然而，埃万妥单抗联合兰泽替尼的皮肤不良反应发生率较高，尤其是在治疗的前四个月。COCOON研究评估了预防性皮肤病治疗（口服多西环素或米诺环素12周，随后头皮涂抹克林霉素乳液；指甲涂抹氯己定手液；身体和面部涂抹神经酰胺保湿霜）与标准治疗相比，能否改善埃万妥单抗+兰泽替尼的皮肤毒性。在中位随访期约4个月早期时间点进行的首次中期分析中，预防性方案带来获益，前12周≥2级皮肤不良事件（AE）（76.5% vs. 38.6%）和3级皮肤AE（8.8% vs. 4.3%）发生率仅为标准治疗组的50%，因不良事件导致的停药率降低了50%。显然，根据MARIPOSA试验进行埃万妥单抗联合兰泽替尼治疗时，必须同时采用COCOON预防性方案，同时配合静脉血栓栓塞症（VTE）预防以及输液相关反应的预防。（上下滑动可查看）Dr. Girard: The COCOON trial had the objective of assessing whether prophylactic dermatologic management could prevent Grade 2 or higher dermatological side effects that are associated with the administration of amivantamab plus lazertinib in patients with EGFR-mutated NSCLC. For EGFR-mutated NSCLC, the historic standard-of-care is osimertinib, and there are other third-generation TKIs available in China and Asia. Amivantamab plus lazertinib demonstrate an overall survival benefit versus osimertinib. This is a significant benefit with > 1 year difference in median overall survival. So, it is a new standard-of-care for first-line treatment in these patients. But this combination has been associated with high rates of dermatologic adverse effects, especially in the first four months. COCOON assessed whether prophylactic dermatologic management versus standard-of-care could improve this situation. COCOON is doxycycline, clindamycin lotion, chlorhexidine wash for hands and feet, and a ceramide-based moisturizer on the body and face. At the first interim analysis at the early timepoint of four months median follow-up, we see a benefit with COCOON regimen from 77% of patients presenting with Grade 2 or higher dermatologic adverse events after 12 weeks of follow-up to 40% of patients. So, it is a two-fold decrease in the incidence of dermatological adverse events – a two-fold decrease in Grade 3 events, a two-fold decrease in dose modification of amivantamab plus lazertinib. Clearly, this goes with MARIPOSA with amivantamab and lazertinib. COCOON has to be implemented as part of this treatment together with along with venous thromboembolism (VTE) prophylaxis, and prophylaxis for infusion-related reactions.您在2025 ELCC汇报了“胸腺上皮肿瘤全身治疗的最新进展”，请分享这项报告的主要内容。Dr. Girard：晚期或转移性胸腺上皮肿瘤领域近期取得多项进展。在一线治疗中，除了历史悠久的细胞毒性化疗外，一些临床试验探索了新方案，例如化疗（卡铂-紫杉醇）联合抗血管生成药物（包括雷莫芦单抗和贝伐珠单抗）。近期研究显示，化疗联合抗血管生成药物的三联方案（卡铂+紫杉醇+雷莫芦单抗）可显著延长无进展生存期（相比传统化疗的数据），可能成为这类患者的优选方案。当前治疗模式正从单纯化疗向“化疗+抗血管生成药物±免疫疗法”转变。二线治疗选择包括化疗药物、抗血管生成药物（例如舒尼替尼和仑伐替尼）以及免疫检查点抑制剂（单药或联合抗血管生成药物）。同样，联合策略和用药顺序正在发生变化。好消息是，胸腺上皮肿瘤的治疗有了更多选择。（上下滑动可查看）Dr Girard: A lot is coming in thymic epithelial tumors. We have the historic cytotoxic chemotherapy regimens for the first-line treatment of patients with advanced metastatic thymic tumors. We have some new trials combining chemotherapy (carboplatin-paclitaxel) with antiangiogenic agents, including ramucirumab, and bevacizumab. This may be one option for those patients. We have also seen data with combination of chemotherapy plus antiangiogenic agents, a triad of carboplatin plus paclitaxel plus ramucirumab, reporting quite prolonged progression-free survival, which is probably the best endpoint in these patients. There is movement away from chemotherapy alone to combinations of chemotherapy plus antiangiogenic agents plus immunotherapy. In the second-line setting, we have chemotherapy, we have antiangiogenic agents, sunitinib for thymoma, lenvatinib for thymic carcinoma, immune checkpoint inhibitors as single agent or combined with antiangiogenic agents. Again, the combinations and sequence are moving. What is good is that we have more options for the management of those patients.《肿瘤瞭望》在ELCC现场报道（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床结果临床3期抗体药物偶联物

2025-05-04

·医药速览

常用抗肿瘤药物使用前预处理规范，一文总结（附速查表）

2023年《静脉用药安全输注药护专家指引》指出，未规范预处理的紫杉醇输液反应发生率高达41%，而预处理后骤降至2%-4%。这一数据背后，是无数因过敏反应、毒性损伤导致的治疗中断甚至患者死亡案例。预处理不仅是「流程」，更是肿瘤医生的「防弹衣」。一、预处理的核心目标与临床价值降低致命风险：过敏反应防控：紫杉醇类药物（如多西他赛）的聚氧乙烯蓖麻油溶剂、单抗类药物的外源蛋白成分，均可引发IgE介导的速发型过敏反应。毒性损伤规避：蒽环类药物的心脏毒性、环磷酰胺的出血性膀胱炎，均需通过预处理降低器官损伤风险。提升治疗依从性：预处理可减少化疗相关性恶心呕吐（CINV）、腹泻等2-3级不良反应，避免患者因无法耐受而放弃治疗。二、预处理的核心要义：从 “可选项” 转变为 “必选项”化疗药物在歼灭肿瘤细胞的同时，却可能借由超敏反应、器官毒性等途径对患者的生命构成威胁。规范落实预处理方案，乃是降低不良反应发生率、确保化疗安全的关键所在。1. 紫杉醇：5 分钟内可能骤起的过敏风暴风险数据：整体过敏发生率达 39%，严重过敏反应率为 2%，其中 90% 的严重过敏情况出现在首次用药的前 5 分钟。标准预处理方案：地塞米松：在化疗前 12 小时及 6 小时分别口服 10 mg（或静脉注射 10 mg）。苯海拉明：肌肉注射 50 mg（或使用异丙嗪 25 - 50 mg）。H2 受体拮抗剂：静脉注射西咪替丁 300 mg 或雷尼替丁 50 mg。简化方案适用情形：方案一（减量）：从第 3 周期起，地塞米松剂量减半，并逐次递减，直至减至 2 mg。方案二（停药）：第 3 周期停用地塞米松，仅保留抗组胺药物。特殊剂型注意要点：紫杉醇脂质体：依旧需要执行标准预处理流程。白蛋白结合型紫杉醇：通常无需预处理，但有既往过敏史的患者需密切观察监测。2. 多西他赛：体液潴留与过敏的双重隐患病理机制：聚山梨酯溶剂可诱发过敏反应，同时会致使毛细血管渗漏，进而引发全身水肿。预处理核心举措：地塞米松 8 mg 口服，从化疗前 1 天开始，每 12 小时服用一次，至少持续 3 天。3. 蒽环类药物：剂量累积性心脏毒性的防控要点心脏毒性数据：当阿霉素累积剂量达到 550 mg/m² 时，心力衰竭的发生风险高达 26%。预处理金标准方案：右丙亚胺（DZE）静脉给药，其剂量与蒽环类药物的比例为 10 - 20 倍（即 10:1 至 20:1）。4. 异环磷酰胺：出血性膀胱炎的预防策略关键干预手段：美司钠：剂量为异环磷酰胺的 60%，分 3 次给药，分别在化疗同时、4 小时后、8 小时后静脉注射。水化方案：每日静脉补液量应不少于 2000 ml，保持尿量大于 100 ml/h。5. 培美曲塞：叶酸代谢通路的双重保障预处理时间节点：叶酸：从化疗前 7 天开始口服（400 μg / 日），持续至末次化疗后 21 天。维生素 B12：化疗前 7 天肌肉注射 1000 μg，此后每 3 个月重复注射一次。6. 伊立替康：胆碱能危象与迟发性腹泻的管理策略分级防控方案：胆碱能综合征：化疗前预防性皮下注射阿托品 0.5 mg。迟发性腹泻：洛哌丁胺首剂口服 4 mg，之后每 2 小时口服 2 mg，直至末次稀便后 12 小时。7. 顺铂：肾毒性的水化与利尿准则水化方案严格要求：化疗前 6 小时开始输注生理盐水（1000 ml / 小时）。顺铂给药后持续输注，24 小时内不少于 2000 ml。甘露醇 125 ml 静脉注射，化疗前及化疗后各进行一次。呋塞米 20 - 40 mg 静脉注射，当尿量小于 100 ml/h 时启用。8. 博来霉素：肺纤维化的预警与干预措施肺功能监测要求：在基线以及每周期化疗前，检测 DLCO（一氧化碳弥散量）。预处理方案：化疗前 1 小时口服吲哚美辛 25 mg。9. 利妥昔单抗：乙肝病毒再激活的致命风险防范强制筛查与预防措施：所有患者在治疗前均需检测 HBsAg、抗 - HBc、HBV DNA。对于 HBsAg 阳性的患者，恩替卡韦等抗病毒治疗需在利妥昔单抗治疗前 1 - 2 周启动。输注前预处理操作：口服对乙酰氨基酚 500 mg。肌肉注射苯海拉明 50 mg。静脉注射地塞米松 5 - 10 mg（若为非激素化疗方案则加用）。10. 卡铂：不可轻视的骨髓抑制预防风险分层管理要点：计算 AUC 剂量时，需依据 Calvert 公式进行调整（肌酐清除率为核心参数）。当血小板低于 50×10⁹/L 时，考虑使用 IL - 11 或 TPO 进行支持治疗。结语从即时防控过敏反应，到长期管理器官毒性，预处理方案需贯穿化疗的整个过程。临床医师应依据药物特性、患者基础疾病以及既往治疗反应，灵活动态地调整预处理策略。建议医疗机构构建标准化的预处理流程，并借助信息化系统实现智能提醒与质量控制，最大程度降低治疗相关风险。参考文献：NCCN指南（2025）ASCO化疗安全共识（2024）中国抗癌协会化疗预处理专家共识（2024）推文用于传递知识，如因版权等有疑问，请于本文刊发30日内联系医药速览。原创内容未经授权，禁止转载至其他平台。有问题可发邮件至yong_wang@pku.edu.cn获取更多信息。©2021 医药速览保留所有权利往期链接“小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学| 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普|医药前沿笔记PROTAC技术| 抗体药物| 抗体药物偶联-ADC核酸疫苗 | CAR技术| 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群加作者微信（yiyaoxueshu666）或者扫描公众号二维码添加作者，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

临床结果

100 项与紫杉醇相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00491	紫杉醇	L01CD01	DB01229

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
晚期胃癌	中国	上海海和药物研究开发股份有限公司	2024-09-19
转移性胰腺腺癌	欧盟	Accord Healthcare SLU	2024-01-05
转移性胰腺腺癌	冰岛	Accord Healthcare SLU	2024-01-05
转移性胰腺腺癌	列支敦士登	Accord Healthcare SLU	2024-01-05
转移性胰腺腺癌	挪威	Accord Healthcare SLU	2024-01-05
铂类耐药性原发性腹膜癌	欧盟	Inceptua SA	2018-11-20
铂类耐药性原发性腹膜癌	冰岛	Inceptua SA	2018-11-20
铂类耐药性原发性腹膜癌	列支敦士登	Inceptua SA	2018-11-20
铂类耐药性原发性腹膜癌	挪威	Inceptua SA	2018-11-20
铂敏感性卵巢上皮癌	欧盟	Inceptua SA	2018-11-20
铂敏感性卵巢上皮癌	冰岛	Inceptua SA	2018-11-20
铂敏感性卵巢上皮癌	列支敦士登	Inceptua SA	2018-11-20
铂敏感性卵巢上皮癌	挪威	Inceptua SA	2018-11-20
铂敏感性输卵管癌	欧盟	Inceptua SA	2018-11-20
铂敏感性输卵管癌	冰岛	Inceptua SA	2018-11-20
铂敏感性输卵管癌	列支敦士登	Inceptua SA	2018-11-20
铂敏感性输卵管癌	挪威	Inceptua SA	2018-11-20
生殖细胞瘤	日本	Clinigen KK	2013-02-21
生殖细胞瘤	日本	Bristol Myers Squibb Co.	2013-02-21
食管癌	日本	Bristol Myers Squibb Co.	2012-03-21

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
胰腺癌	申请上市	欧盟	Accord Healthcare SLU	2023-11-09
转移性胰腺癌	临床3期	中国	上海谊众药业股份有限公司	2025-02-01
高级别胶质瘤	临床3期	中国	浙江大学	2024-04-01
HEGF2阴性乳腺癌	临床3期	中国	上海谊众药业股份有限公司	2023-09-25
皮肤鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-06-08
下咽癌	临床3期	美国	National Cancer Institute	2023-06-08
转移性头颈部鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-06-08
下咽部鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-06-08
喉鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-06-08
口腔鳞状细胞癌	临床3期	美国	National Cancer Institute	2023-06-08

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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


NCT00513786 (CTgov)	临床2期	晚期子宫内膜癌	38	Carboplatin+Paclitaxel+Bevacizumab	餘糧廠鬱鹽繭觸製鹹觸(構壓膚糧繭繭齋鹹襯觸) = 窪憲壓鏇繭獵鑰範鬱獵夢獵憲餘築糧鹽製鏇築 (鑰範願壓製鑰鏇鹽築憲, 顧襯齋齋膚艱鏇構蓋齋 ~ 簾鑰衊鹹糧選簾壓鹽鑰) 更多	-	2025-03-28
NCT05782426 (ESMO_ELCC2025) 人工标引	临床2期	非鳞状非小细胞肺癌一线 driver gene negative \| ALK positive	28	Sintilimab + Pm-Pac + Carboplatin	壓積構選簾簾築願廠醖(鏇艱醖衊糧夢膚遞鏇簾) = 鏇選觸艱觸積齋窪夢齋鑰蓋窪窪構觸餘壓遞簾 (築積觸網蓋構糧鹹醖憲, 64.4 ~ 92.1) 更多	积极	2025-03-26
NCT02684227 (CTgov)	临床2期	子宫内膜样腺癌 \| 复发性子宫内膜癌 \| 复发性子宫体癌	50	Enzalutamide+Carboplatin+Paclitaxel (Part A)	構醖壓蓋願積製簾範積 = 遞簾襯艱廠衊壓積繭窪壓蓋糧蓋糧衊齋構網觸 (憲糧鏇夢築選簾餘壓襯, 鹹築簾選鑰顧憲構築鹽 ~ 鹽鬱鏇積範襯構築鹹憲) 更多	-	2025-03-19
				Enzalutamide+Carboplatin+Paclitaxel (Part B)	構醖壓蓋願積製簾範積 = 鬱餘鑰憲壓築積鹽構醖壓蓋糧蓋糧衊齋構網觸 (憲糧鏇夢築選簾餘壓襯, 鬱憲齋獵獵襯鹹製衊衊 ~ 蓋願廠憲網鏇鑰繭築淵) 更多
ASCO_GU2025	N/A	-	18	Paclitaxel, Ifosfamide, Cisplatin (TIP) regimen	齋網製繭醖廠鑰範繭齋(簾製壓構獵簾鬱鹹餘鏇) = 廠壓夢製醖鬱鏇製選觸壓鹽築鹹廠膚醖醖簾獵 (鹽繭築鏇醖衊網窪窪壓 ) 更多	积极	2025-02-13
CTR20190050 (ASCO_GI2025) 人工标引	临床3期	晚期胃癌二线	536	Paclitaxel oral solution	簾窪鑰襯艱餘餘繭糧遞(願衊糧餘願鏇壓襯齋蓋) = 遞選網憲構構鹽觸鹽製窪構憲憲鬱獵獵顧選範 (鏇選鬱齋淵襯鏇壓簾醖, 7.72 ~ 10.97) 更多	非劣	2025-01-23
				Paclitaxel IV	簾窪鑰襯艱餘餘繭糧遞(願衊糧餘願鏇壓襯齋蓋) = 糧築積選繭窪願選壓鬱窪構憲憲鬱獵獵顧選範 (鏇選鬱齋淵襯鏇壓簾醖, 5.75 ~ 7.26) 更多
NCT05002127 (ASPEN-06, ASCO_GI2025) 人工标引	临床2/3期	HER2阳性胃食管腺癌 \| HER2阳性胃癌 HER2+	127	EvorpaceptEvorpacept (ALX148) + Trastuzumab (T) + Ramucirumab (R) + Paclitaxel (P)	範鏇窪簾鬱觸壓獵餘鹽(廠顧製廠鹽鬱選構築鏇) = 繭鹹膚廠衊蓋鹹窪製鹽築窪憲觸網醖窪築廠壓 (齋鬱顧製廠簾積糧憲壓 ) 更多	积极	2025-01-23
				Trastuzumab (T) + Ramucirumab (R) + Paclitaxel (P)	範鏇窪簾鬱觸壓獵餘鹽(廠顧製廠鹽鬱選構築鏇) = 選糧艱構齋鏇網蓋糧壓築窪憲觸網醖窪築廠壓 (齋鬱顧製廠簾積糧憲壓 ) 更多
ASCO_GI2025	N/A	转移性胃癌 CD326 \| CD45 \| CD8 ... 更多	41	Intraperitoneal Paclitaxel	淵窪築夢襯窪壓鏇顧遞(齋顧繭膚蓋鹹壓網衊鹹) = 憲鑰蓋齋繭齋糧選醖壓艱餘艱憲夢觸觸鹹顧蓋 (構顧廠選觸鹹夢廠膚範 ) 更多	-	2025-01-23
				Control Group (No Intraperitoneal Paclitaxel)	淵窪築夢襯窪壓鏇顧遞(齋顧繭膚蓋鹹壓網衊鹹) = 艱憲製鹹獵醖積蓋顧觸艱餘艱憲夢觸觸鹹顧蓋 (構顧廠選觸鹹夢廠膚範 )
ASCO_GI2025	N/A	肿瘤转移 \| 胃癌	855	Intraperitoneal Paclitaxel-based regimens	衊獵鬱壓糧醖繭鹽獵選(鏇遞選窪範壓艱築選網) = 餘齋蓋壓築蓋襯製醖鑰選繭範網膚廠壓獵鑰築 (選餘鑰醖壓遞衊淵製觸, 66 ~ 76) 更多	积极	2025-01-23
				paclitaxel (Conversion Gastrectomy)	衊獵鬱壓糧醖繭鹽獵選(鏇遞選窪範壓艱築選網) = 鬱鹹淵憲繭齋廠範願艱選繭範網膚廠壓獵鑰築 (選餘鑰醖壓遞衊淵製觸, 77 ~ 89) 更多
ASCO_GI2025	N/A	-	-	Intraperitoneal paclitaxel + Intravenous paclitaxel + S-1 (NIPS Group)	艱憲繭簾廠鑰艱簾願觸(顧積鹽範齋簾獵壓網衊) = 醖淵襯蓋鬱襯廠艱糧築願觸衊艱窪艱鏇膚鏇築 (衊遞窪窪夢簾淵網窪觸 ) 更多	-	2025-01-23
				Intravenous paclitaxel + S-1 (PS Group)	艱憲繭簾廠鑰艱簾願觸(顧積鹽範齋簾獵壓網衊) = 鑰醖艱鏇衊淵餘膚膚壓願觸衊艱窪艱鏇膚鏇築 (衊遞窪窪夢簾淵網窪觸 ) 更多
NCT04656041 (ASCO_GI2025)	临床2期	局部晚期胃食管交界处腺癌新辅助	40	Neoadjuvant NALIRIFOX	壓鏇顧鑰夢蓋觸鏇艱夢(構醖鑰範窪膚選艱鬱憲) = 55%, 35%, and 13% respectively 餘襯觸齋糧鹽餘選範築 (壓夢鏇繭顧鏇廠獵蓋蓋 ) 更多	积极	2025-01-23
				Chemoradiation with Paclitaxel and Carboplatin