Over the past decades, healthcare systems face significant challenges to meet the needs of an aging population due to progressive debility, functional decline and chronic diseases development. While there is a growing appreciation of the potential impact of mTOR inhibitors on slowing aging processes, preventing chronic disease and prolonging healthy lifespan, a major challenge in developing clinical trials to establish the clinical efficacy of mTOR inhibitors is the absence of pharmacokinetics (PK) and pharmacodynamics (PD) data in older adults. The proposed study will provide the foundation for future clinical trials assessing the role of mTOR inhibitors on aging related indications

开始日期2025-05-01

申办/合作机构

The University of Texas Southwestern Medical Center

[+2]

NCT04199026 / Not yet recruiting早期临床1期IIT

Pilot Trial of an Implantable Microdevice for In Vivo Drug Sensitivity Testing in Patients With Sarcomas

This early phase I trial studies the side effects of implanting and removing a microdevice in patients with sarcomas that have spread to other places in the body (metastatic) or have come back (recurrent). Microdevices are rice-sized devices that are implanted into tumor tissue and are loaded with 10 different drugs that are delivered at very small doses, or "microdoses," which may only affect a very small, local area inside the tumor. The purpose of this study is to determine which drugs delivered in the microdevice affect tumor tissue in patients with sarcomas.

开始日期2025-01-31

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT06658093 / Not yet recruiting早期临床1期IIT

RESTOR [Rapamycin and Everolimus Study Towards Older Rejuvenation]: An Exploratory PK/PD Study of mTOR Inhibition in Older Human Subjects

As people get older, there are changes in their cells and tissues that may affect their ability to function. This can lead to increased death and age-associated disorders, like heart disease, cancer, and Alzheimer's disease. Studies in animal models have been able to identify drugs that slow the aging process, leading to a longer, healthier life. This study is focused on one such family of drugs, called mTOR inhibitors, and the investigators' goal is to test two of these drugs, Rapamycin (Sirolimus) and Everolimus (Afinitor), in healthy older adults to find a dose and dose timing that can be used to safely inhibit mTOR to the levels seen in young healthy persons. The investigators expect that the dose that works well in women may differ from the one that is best in men, so it is important to include both sexes in this research.

开始日期2025-01-01

申办/合作机构

University of Texas Health Science Center At San Antonio

[+1]

100 项与依维莫司相关的临床结果

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100 项与依维莫司相关的转化医学

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100 项与依维莫司相关的专利（医药）

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8,557

项与依维莫司相关的文献（医药）

2025-12-01·IMMUNOLOGIC RESEARCH

RAD001-mediated mTOR targeting in human monocyte-derived dendritic cells shifts them toward an immunogenic phenotype

Article

作者: Masoumi, Javad ; Hatami-Sadr, Amirhossein ; Baradaran, Behzad ; Hemmat, Nima ; Alipour, Shiva ; Alizadeh, Nazila ; Vaysi, Edris ; Naseri, Bahar

Dendritic cells (DCs) are essential for promoting T lymphocyte responses since they are specialist antigen-presenting cells. In order to maintain tolerance or initiate immune responses, DCs must be activated in a balanced and regulated manner via diverse signaling pathways. By using a variety of pharmacological components, we can interfere with their different signaling pathways such as the mammalian target of rapamycin (mTOR) to appropriately modulate DC activity. In the current study, we administered RAD001 to DCs to examine the impact of mTOR inhibition on both the maturation stage and the expression of inflammatory and anti-inflammatory molecules in DCs. Pure monocytes were cultivated and stimulated with GM-CSF and IL-4 to generate immature DCs, which were then treated with RAD001. The phenotype of the DCs was determined by labeling surface markers and analyzing them using flow cytometry. Afterward, real-time PCR was carried out to evaluate the expression of inflammatory and anti-inflammatory genes. The administration of RAD001 to DCs led to a significant upregulation in the gene expression of inflammatory molecules such as IL-12, IL-1β, tumor necrosis factor (TNF)-α, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB). Conversely, RAD001 treatment resulted in a decrease in the gene expression of anti-inflammatory factors IL-10 and indoleamine 2,3-dioxygenase (IDO). However, the expression of differentiation and antigen presentation-related markers CD11c and human leukocyte antigens (HLA)-DR in RAD001-treated DCs was lower and higher compared to the control group that did not receive the treatment, respectively. Taken together, our findings indicated that RAD001 treatment of DCs can be a promising therapeutic approach for the generation of immunogenic DCs in order to barricade tumor growth. However, there is a need for further investigation to evaluate the impacts of mTOR inhibition by RAD001 in DCs on cellular immune responses in vitro and in vivo.

2025-03-01·BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

High MICAL-L2 promotes cancer progression and drug resistance in renal clear cell carcinoma cells through stabilization of ACTN4 following vimentin expression

Article

作者: Min, Pengxiang ; Zhao, Weizhen ; Mao, Yixin ; Ye, Fengwen ; Zhang, Yujie ; Zhao, Mingyu ; Qi, Chenxiang ; Du, Jun ; Xia, Tianxiang

Targeted therapies persist as the conventional method of treatment of kidney clear cell carcinoma (KIRC). However, resistance to these drugs emerges as a significant impediment to the management of renal cancer. MICAL-L2 plays a pivotal role in cytoskeleton rearrangement. This study sought to elucidate the clinical relevance of MICAL-L2 in KIRC and its regulatory mechanism driving cancer progression and resistance to therapy. TCGA data mining was utilized to assess the expression of MICAL-L2 in samples from patients with KIRC. Kaplan-Meier analysis and immunohistochemistry were employed to explore the clinical significance of MICAL-L2. In vitro experiments, including assays for wound healing and Transwell migration, CCK-8, EDU staining, RT-PCR, flow cytometry, and co-immunoprecipitation analysis were conducted to investigate the effects of MICAL-L2 on the drug sensitivity of KIRC cells and to elucidate the molecular mechanisms involved. The results showed that MICAL-L2 was overexpressed in KIRC tissues. High levels of MICAL-L2 were associated with poor survival and a poor response to drug therapy among patients with KIRC. Overexpression of MICAL-L2 stimulated cell migration, proliferation, and rendered KIRC cells insensitive to sunitinib and everolimus, two traditional therapies for KIRC. Furthermore, MICAL-L2 overexpression accelerated cancer progression and resistance to therapy in KIRC cells by interacting with its downstream regulator α-actinin-4 (ACTN4) in a Rab13-dependent manner, which reduced the degradation of ACTN4, leading to increased Vimentin expression. All these findings indicate that MICAL-L2 plays a crucial role in the progression of KIRC and suggest that MICAL-L2 may serve as a potential therapeutic target for KIRC treatment.

2025-02-01·CURRENT CANCER DRUG TARGETS

Screening miRNAs to Hinder the Tumorigenesis of Renal Clear Cell Carcinoma Associated with KDR Expression

Article

作者: Suseela, Rangaraj ; Miji, Thandaserry Vasudevan ; Bharathi, Muruganantham ; Muthusami, Sridhar ; Almoallim, Hesham S. ; Kaviyaprabha, Rangaraj ; Thangaleela, Subramanian ; Sivakumar, Priyadarshini

Introduction::

This study delved into the role of Kinase Insert Domain Receptor (KDR) and its associated miRNAs in renal cell carcinoma through an extensive computational analysis. The potential of our findings to guide future research in this area is significant.

Methods::

Our methods, which included the use of UALCAN and GEPIA2 databases, as well as miRDB, MirDIP, miRNet v2.0, miRTargetLink, MiEAA v2.1, TarBase v8.0, INTERNET, and miRTarBass, were instrumental in identifying the regulation of miRNA associated with KDR expression. The predicted miRNA was validated with the TCGA-KIRC patients’ samples by implementing CancerMIRNome. The TargetScanHuman v8.0 was implemented to identify the associations between human miRNAs and KDR. A Patch Dock server analyzed the interactions between hsa-miR-200b-3p-KDR and hsa-miR-200b-3p with KDR.

Results::

The KDR expression rate was investigated in the Kidney Renal Cell Carcinoma (KIRC) samples, and adjacent normal tissues revealed that the expression rate was significantly higher than the normal samples, which was evident from the strong statistical significance (P = 1.63e-12). Likely, the KDR ex-pression rate was estimated as high at tumor grade 1 and gradually decreased till the metastasis grade, reducing the survival rate of the KIRC patients. To identify these signals early, we predicted a miRNA that could trigger the expression of KDR. Furthermore, we uncovered the potential associations between miR-200c-3p expressions by regulating KDR towards the progression of KIRC.

Discussion::

Upon examining the outcome, it became evident that miR-200c-3p was significantly down-regulated in KIRC compared to the normal samples. Moreover, the negative correlation was obtained for hsa-miR-200c-3p (R = - 0.276) along with the KDR expression describing that the increased rate of hsa-miR-200c-3p might reduce the KDR expression rate, which may suppress the KIRC initiation or progres-sion.

Conclusion::

The in-silico analysis indicated that the significant increase in KDR expression during the initiation of KIRC could serve as an early diagnostic marker. Moreover, KDR could be utilized to identify advancements in KIRC stages. Additionally, hsa-miR-200c-3p was identified as a potential regulator capable of downregulating and upregulating KDR expression among the 24 miRNAs screened. This find-ing holds promise for future research endeavors. Concurrent administration of the FDA-approved 5-fluor-ouracil with KIRC drugs, such as sorafenib, zidovudine, and everolimus, may have the potential to en-hance the therapeutic efficacy in downregulating hsa-miR-200c-3p. However, further in vitro studies are imperative to validate these findings and gain a comprehensive understanding of the intricate regulatory interplay involving hsa-miR-200c-3p, KDR, 5-fluorouracil, and other FDA-approved drugs for the treat-ment of KIRC. This will facilitate the identification of KIRC stage progression and its underlying pre-ventative mechanisms.

524

项与依维莫司相关的新闻（医药）

2024-12-24

·医脉通

生命篇章：吡咯替尼温暖照亮曲妥珠单抗耐药患者治愈之路

导读在生命的舞台上，34岁的毛女士，一位慈爱的母亲，面对HR-/HER2+早期乳腺癌的诊断，她选择了勇敢地与之抗衡。治疗的过程并非一帆风顺，病魔最终还是将毛女士推向了晚期乳腺癌的深渊。在本期【“艾”的例量，伴“妮”同行】栏目中，我们将一同走进毛女士的生命旅程，在曲妥珠单抗治疗的希望之光骤然黯淡之时，是吡咯替尼的曙光，再次为她点燃了新的希望，让她得以走向更远的未来。母爱如山，不惧命运的波涛 2019年，一场突如其来的风暴席卷了毛女士的生活。她被诊断为HR-/HER2+乳腺癌，pT2N0M0，ⅡA期。对于一个两岁孩子的母亲来说，这无疑是沉重的打击，但正因为是一名母亲，她不能轻易认输。在医生的指导下，她以乐观和坚强的姿态，开始了与病魔的斗争。毛女士先后接受了EC*4-TH*4化疗、放疗，以及维持1年的曲妥珠单抗靶向治疗。2020年6月4日，随着最后一次的曲妥珠单抗治疗结束，毛女士的治疗之旅终于告一段落。然而，正当毛女士以为生活已逐渐回到正轨时，肝转移的诊断如同晴天霹雳再一次打乱了她的人生。2021年，在复旦大学附属肿瘤医院的进一步检查中，毛女士被确诊为HR+/HER2+乳腺癌肝转移。毛女士的内心经历了剧烈的波动，她感到恐惧、无助，但更多的是对儿子未来的担忧。然而，作为一名母亲，她知道她必须成为儿子的坚强后盾。她告诉自己，无论多么艰难，她都要为了儿子，为了这个家，继续战斗下去。在家人的鼓励和支持下，毛女士开始寻找新的治疗希望。她和家人都坚信，一定会有一线生机。图1 2021年8月，PET-CT提示肝右上叶后段（VII段）转移灶，FDG代谢增高；MRI结果显示:肝S7段结节，约15mm*12mm，T1W1低信号，T2W1稍高信号，增强后强化，另见肝脏微小结节长T1长T2信号，界清，无强化一项研究，重燃生命的希望在曲妥珠单抗治疗结束后的第10个月，肝脏转移成为了毛女士的抗癌新战场。既往研究数据提示，曲妥珠单抗辅助治疗后，大约有15%的患者在8年内出现疾病进展；而在治疗结束后一年内，这一比例大约是5%1。遗憾的是，毛女士成为了那不幸的少数之一。在病魔面前，命运是那么不可预测。在早期曲妥珠单抗经治后进展的群体中，毛女士这类无病间期（DFI）较短的患者，往往表现为更具侵袭性的疾病特征。针对这类曲妥珠单抗原发性耐药患者，目前公布的研究数据较为有限，且结果并不尽如人意。既往两项针对曲妥珠单抗原发性耐药患者的Ⅲ期研究显示，接受阿法替尼联合长春瑞滨治疗的曲妥珠单抗原发性耐药患者中位无进展生存期（mPFS）仅为5.5个月；接受依维莫司联合曲妥珠单抗、长春瑞滨的曲妥珠单抗原发性耐药患者mPFS为7.0个月2,3。这些数据揭示了曲妥珠单抗原发性耐药患者存在显著未被满足的治疗需求，亟需探索最佳治疗策略和药物，以改善这些患者的预后和生活质量。天无绝人之路，一则消息为毛女士的治疗带来了一线生机。PICTURE研究正在招募入组患者。这是由复旦大学附属肿瘤医院胡夕春教授牵头的一项针对曲妥珠单抗原发性耐药患者的单臂、多中心Ⅱ临床研究，纳入早期或晚期治疗期间曲妥珠单抗治疗不敏感的患者，接受吡咯替尼和卡培他滨的治疗。毛女士恰好满足PICTURE研究的入组标准，在医生的建议和鼓励下，她说道：“我愿意尝试，为了能有更多的时间陪伴我的孩子。” 吡咯替尼联合卡培他滨，创造生命的奇迹 2021年9月7日，完善相关检查后的毛女士顺利加入临床试验，正式开始吡咯替尼联合卡培他滨治疗。用药2周期后，毛女士的肝S7段结节从15mm*12mm缩至约7mm*8mm，达到部分缓解（PR）；用药4周期后，肝S7段结节缩至约7.5mm。这一奇迹，不仅记录在检查报告单上，更深深地刻在了毛女士的心中。她看着逐渐好转的复查结果，更加坚定了自己的信念：继续战斗，永不放弃！2022年4月，当地医院复查结果提示，毛女士的肝S7段类结节未见，达到完全缓解（CR）。经过了8个月的吡咯替尼联合卡培他滨治疗，她成功地扭转了病情，打了一个漂亮的翻身仗。2022年9月，PET-CT复查结果提示，毛女士的肝右上叶后段转移灶消失，疗效CR。2024年10月是毛女士最近的一次复查，影像学检查显示，毛女士各方面情况稳定，并无新病灶。这来之不易的完全缓解，让毛女士喜极而泣。这意味着，在PICTURE研究的帮助下，她从病魔手中抢夺回更多陪伴家人的时间了！她可以继续看着孩子成长了！图2 2022年9月PET-CT显示肝右上后叶段（VII段）转移灶消失不仅如此，吡咯替尼联合卡培他滨的治疗方案整体耐受性良好。治疗初期，毛女士曾出现3级腹泻，但在医生的建议下使用易蒙停与静脉补液后，腹泻得到了有效控制，目前仅偶尔出现腹泻。时至今日，毛女士的PFS已超3年，至今仍在服药。这不仅是她对生命的坚持，更是她对家庭的承诺。吡咯替尼联合卡培他滨的治疗方案，以其良好的耐受性和持久的疗效，为毛女士带来了长期的生存获益。毛女士的主诊医生，PICTURE研究的sub-I曹君医生分享到：“PICTURE研究的完整报告已于2023年8月10日在《BMC Medicine》期刊上发表。研究结果显示，中位随访时间20.1个月时（范围：1.3-38.2），总人群的mPFS达到11.8个月（95%CI，8.4-15.1），达到了主要研究终点。其中，像毛女士一样的曲妥珠单抗辅助治疗后12个月内进展的患者（亚组B）mPFS更是达到17.8个月（95%CI，13.8-NR）之久4。2023年ESMO大会期间，PICTURE研究公布了最新的中位总生存期（mOS）数据。结果显示了吡咯替尼联合卡培他滨在曲妥珠单抗原发性耐药的HER2阳性晚期患者中的长期疗效，其中亚组B的mOS最长，达41.7个月（95%CI，38.5-NR）5。此外，吡咯替尼联合卡培他滨用药安全性良好，未发现新的安全性事件，没有患者因不良事件停用吡咯替尼4。” 图3 PICTURE研究中总人群的mPFS 图4 PICTURE研究中亚组B的mOS “PICTURE研究是目前CSCO指南推荐的主流抗HER2治疗方案中，首个在曲妥珠单抗原发性耐药这一难治人群中开展前瞻性临床研究并取得惊喜结果的方案。其中，亚组B人群在临床试验中通常被归类为曲妥珠原发性耐药患者，其17.8个月的PFS可能并不低于既往报道的HER2阳性乳腺癌晚期一线治疗PFS4。与此同时，亚组B和亚组C的mPFS提示，曲妥珠单抗治疗期间进展的患者和治疗结束后进展的患者可能涉及不同的耐药机制，可进一步探索。综合来看，吡咯替尼满足了曲妥珠原发性耐药患者的临床需求，为其提供了一个安全有效的治疗方案。”曹君医生在采访中说到。坚守治疗，吟唱希望之歌谁无暴风劲雨时，守得云开见月明。3年多的治疗坚守，也让毛女士的生活状态越来越好。如今，她的体力已基本恢复，足以照顾正在上小学的孩子。除了每日需按时服药和定期前往医院检查外，疾病对她的生活影响已微乎其微。她特别感激医生的帮助，让她有机会参与PICTURE临床试验，吡咯替尼联合卡培他滨的治疗方案为她的生命带来了新的光明。同时，她也深感幸运，因为家人的支持和鼓励，让她在面对疾病时能够保持乐观的心态和愉悦的心情。她相信，这也是她治疗效果良好的重要因素之一。针对曲妥珠单抗治疗失败后的HER2阳性晚期乳腺癌解救治疗，最新的《中国临床肿瘤学会（CSCO）乳腺癌指南》推荐了酪氨酸激酶抑制剂（TKI）和抗体-药物偶联物（ADC）等多种治疗选择，但并不是所有治疗方案都公布了原发耐药群体的数据6。对于曲妥珠单抗原发性耐药患者，ADC的治疗有效性有待临床研究进一步验证。而PICTURE研究的疗效充分说明，吡咯替尼联合卡培他滨能够为曲妥珠单抗经治患者带来长期生存获益。该研究结果为曲妥珠单抗经治人群的用药提供了强有力的循证医学证据，并填补了疾病特征更为凶猛的原发耐药这类人群的治疗空白。结语在医学的探索与进步中，吡咯替尼的应用重新为毛女士的家庭带来了温暖与光明。她的故事，是无数乳腺癌患者抗争的缩影，也是医学研究不断前行的动力。毛女士的坚持和乐观，让我们相信，即使在最黑暗的时刻，希望之光也从未远离。专家简介曹君教授复旦大学附属肿瘤医院肿瘤内科副主任医师上海市抗癌协会乳腺癌专业委员会青年委员上海市抗癌协会癌症康复与姑息治疗专业委员会委员上海市女医师协会乳腺专委会委员上海市抗癌协会疑难肿瘤专委会委员中国医药教育协会医学国际交流促进工作委员会常委中国生物工程学会肿瘤药物基因组学专业委员会委员上海市中西医结合学会甲乳外科专委会委员中国医药教育协会肿瘤转移专业委员会委员中国女医师协会乳腺专委会委员长江学术带乳腺联盟（YBCSG）委员《中国癌症杂志》审稿专家参与编写《肿瘤科常见诊疗问题问答》、《乳腺肿瘤治疗学》、《肿瘤内科治疗手册》、《肿瘤内科化疗方案手册》等多部书籍参考资料： 1. Eight-year data from APHINITY study show Roche’s Perjeta-based regimen continues to reduce the risk of disease returning for people with HER2-positive early breast cancer. News release. Roche. July 14, 2022. Accessed July 14, 2022. bit.ly/3uOrzSj 2. Harbeck N, Huang C-S, Hurvitz S, et al. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016;17(3):357–66. 3. André F, O’Regan R, Ozguroglu M, et al. Everolimus for women with trastuzumabresistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014;15(6):580–91. 4. Cao J, Teng Y, Li H, et al. Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer (PICTURE): a single-arm, multicenter phase 2 trial. BMC Med. 2023 Aug 9;21(1):300. doi: 10.1186/s12916-023-02999-0. 5. Xichun Hu, et al. Pyrotinib plus capecitabine for trastuzumab-resistant, HER2-positive advanced breast cancer:updated survival results from the phase 2 PICTURE tria. 2023 ESMO FPN: 424P. 6. 2024 CSCO乳腺癌指南. END 医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。

临床3期临床结果

2024-12-20

·复宏汉霖

2024 APA/JPS/CAP/IAP年会口头报告 | 复宏汉霖H药汉斯状®胰腺癌治疗最新研究数据发布

近日，由美国胰腺学会/日本胰腺学会/中国胰腺病学会/国际胰腺病协会（APA/JPS/CAP/IAP）四大胰腺顶级学会联合举办的2024年第55届胰腺病学会年会在美国夏威夷成功举行，该会议是全球胰腺病学领域最具影响力的学术盛会之一。会上，四川大学华西医院曹丹教授团队口头报告了斯鲁利单抗联合化疗及放疗一线治疗胰腺癌的II期研究数据。 H药汉斯状®（通用名：斯鲁利单抗注射液）为复宏汉霖自主研发的重组人源化抗PD-1单抗注射液，也是全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，已在中国和多个东南亚国家获批，惠及患者约9万人。此外，H药一线治疗广泛期小细胞肺癌（ES-SCLC）的上市申请也已获得欧盟EMA受理，有望于2025年获得批准。聚焦肺癌和消化道肿瘤等瘤种，复宏汉霖积极推进H药与公司其他产品的协同以及与创新疗法的联合，在全球同步开展10余项肿瘤免疫联合疗法临床试验，于中国、美国、土耳其、波兰、格鲁吉亚等国家和地区累计入组超4600人。消化道肿瘤是我国和全球范围内高发病率和高死亡率的瘤种，主要包括结直肠癌、胃癌、肝癌、食管癌、胰腺癌和胆囊胆管癌。根据2022年全球癌症统计数据，全球约有490万例新发消化道癌症病例和332万例死亡病例，占所有癌症发病例约25%，占癌症相关死亡的34%以上[1]。针对消化道肿瘤，H药联合化疗治疗不可切除局部晚期/复发或转移性食管鳞癌(ESCC)的一线治疗方案已于2023年9月获得中国国家药监局（NMPA）批准上市，为我国食管鳞癌患者带来了免疫治疗新选择。与此同时，该产品在胃癌新辅助/辅助方面已进入III期临床研究，有望使胃癌患者在前线便从肿瘤免疫疗法中获益。以下为此次发布的详细信息：论文题目：AG方案（白蛋白紫杉醇+吉西他滨）联合斯鲁利单抗及立体定向体放疗（SBRT）一线治疗局晚期及转移性胰腺癌的II期临床研究牵头主要研究者：曹丹四川大学华西医院报告人：成科，四川大学华西医院报告时间：2024年12月11日（夏威夷时间）研究设计：研究采用AG方案（白蛋白紫杉醇+吉西他滨）联合斯鲁利单抗及 SBRT （ICSBRT）作为 mPDAC（转移性胰腺导管腺癌）的一线治疗方案。经筛选合格的受试者将接受吉西他滨、白蛋白紫杉醇联合斯鲁利单抗治疗，每21天为一个周期。第2周期将同步进行SBRT。白蛋白紫杉醇 125mg/m2，ivgtt，day1、8，每21天重复；吉西他滨 1000mg/m2，ivgtt，day1、8，每21天重复；斯鲁利单抗 200mg，ivgtt，day1，每21天重复；SBRT ：原发灶6.6Gy×5次，转移灶 8Gy×3次，从第 2 周期开始。主要终点是 6 个月无进展生存率（6m-PFS%）。次要终点包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和安全性等。结果：截至 2024 年10月，共纳入44名患者进行分析。研究的主要终点6个月的PFS率达74.48%；次要终点mPFS为8.6个月， mOS为15.5个月。次要终点: 研究的ORR为75%，DCR为100%。肿瘤目标病灶消退情况：N=44，所有患者在目标病灶上均出现肿瘤消退，33 例患者达到 PR/CR。亚组生存分析：入组前是否接受过根治性切除手术，PFS和OS均无显著性差异。安全性分析：研究中3级以上TEAEs发生率为79.55%，没有发生严重的TEAEs，常见的TEAEs为厌食，中性粒细胞减少，白细胞减少，疲劳，呕吐，皮疹和恶心。结论：这项 II 期研究的中期结果达到了研究预设的主要终点，6 个月PFS率为 74.48%，ORR 为 75%，DCR 为 100%，中位 PFS 为 8.6 个月，中位 OS 为 15.5 个月，安全性可控。这是第一个报道 ICIs 联合 SBRT 联合化疗治疗一线 mPC 的良好临床疗效和安全性的机构。免疫联合放化疗（ICSBRT）显示出有希望的疗效，这支持将这种联合治疗作为 mPDAC 患者的一线治疗。关于复宏汉霖复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已有6款产品在中国获批上市，3款产品在国际获批上市，25项适应症获批，4个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，公司商业化生产基地已相继获得中国、欧盟和美国GMP认证。复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖50多个分子，并全面推进基于自有抗PD-1单抗H药汉斯状®的肿瘤免疫联合疗法。截至目前，公司已获批上市产品包括国内首个生物类似药汉利康®（利妥昔单抗）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）以及汉奈佳®（奈拉替尼），此外，创新产品汉斯状®（斯鲁利单抗）已获批用于治疗微卫星高度不稳定（MSI-H）实体瘤、鳞状非小细胞肺癌、广泛期小细胞肺癌、食管鳞状细胞癌和非鳞状非小细胞肺癌，并成为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗。公司亦同步就16个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。 Latest Results of Serplulimab in The Field of Pancreatic Cancer Released In APA/JPS/CAP/IAP 2024 Annual Meeting in Oral Presentation Recently，one of the most distinguished meeting in the field of pancreatology—the APA/JPS/CAP/IAP 2024 Annual Meeting, jointly organized by the American Pancreatic Association (APA), the Japan Pancreas Society (JPS), the Chinese Pancreatic Association (CAP) and the International Association of Pancreatology (IAP), was successfully held in Hawaii, USA. At this congress, Professor Dan Cao’s team from West China Hospital of Sichuan University reported the results of a phase 2 clinical trial of serplulimab in combination with chemotherapy and radiotherapy for the first-line treatment of pancreatic cancer in oral presentations. HANSIZHUANG (serplulimab), Henlius’ first self-developed innovative Anti-PD-1 mAb, is the world’s first anti-PD-1 mAb for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Up to date, it has been approved in China and several Southeast Asian countries, benefiting over 90,000 patients. Furthermore，the marketing applications of the first-line treatment for ES-SCLC is under review by the European Medicines Agency (EMA), which is expected to be approved in 2025. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. The company has initiated more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications with more than 4,600 subjects enrolled in China, the U.S., Turkey, Poland, Georgia and other countries and regions. Gastrointestinal tumors are characterized by high incidence and mortality rates both in China and globally. The main types include colorectal cancer, gastric cancer, liver cancer, esophageal cancer, pancreatic cancer, and gallbladder & bile duct cancer. According to global cancer statistics for 2022, there were approximately 4.90 million new cases and 3.32 million deaths due to gastrointestinal cancers worldwide, accounting for about 25% of all new cancer cases and more than 34% of cancer-related deaths[1]. In terms of gastrointestinal cancer, HANSIZHUANG in combination with chemotherapy for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic ESCC has been approved by the China National Medical Products Administration (NMPA) in September 2023, providing a new treatment option for patients with ESCC. Meanwhile, HANSIZHUANG has led the way with a phase 3 clinical study on neoadjuvant/adjuvant therapies for gastric cancer, striving to benefit gastric cancer patients from the early line of immunotherapy. The detailed results of the study released at APA/JPS/CAP/IAP 2024 Annual Meeting are as follows: Title: Phase II Trial of Gemcitabine plus nab-paclitaxel (GnP) Combined with Serplulimab and SBRT for Metastatic Pancreatic Cancer As the First-line Treatment Leading PI: Dan Cao, West China Hospital of Sichuan University Presenter: Ke Cheng, West China Hospital of Sichuan University Study Design: Immunotherapy (Serplulimab), chemotherapy (GnP) plus SBRT (ICSBRT) as the first-line treatment for mPDAC. The eligible patients without previous treatment, will be administered gemcitabine 1000mg/m2 and nab-paclitaxel 125mg/m2 intravenously on day 1 and day 8 every 3 weeks. Serplulimab 200mg will be administered intravenously on day 1 every 3 weeks, and SBRT delivering 5 fractions of 6.6 Gy to primary tumor or 3 fractions of 8 Gy to metastatic lesion in cycle 2. The primary endpoint was 6-month progression free survival (PFS) rate. The secondary endpoints included overall survival (OS), PFS, ORR, DCR, and safety outcomes. Results: Follow up to October 2024, forty-four patients were enrolled. Primary endpoint：The 6-months PFS rate calculated through KM curve is 74.48%. Secondary endpoints: an mPFS of 8.6 months and an mOS of 15.5 months. Secondary endpoints: The ORR of the study was 75%, and the DCR was 100%. Tumor regression ratio: Waterfall plot of the best percent change in target lesion diameter from baseline, colored according to best of response (n=44). All patients experienced tumor regression in the target lesion, 33 patients achieved PR/CR. Subgroup survival analysis: according to whether received radical resection before enrollment. No significant difference was observed in PFS and OS. Safety analysis: the incidence of grade 3 or higher TEAEs was 79.55%, with no serious TEAEs occurring. The frequent TEAEs included anorexia, neutropenia, leukopenia, fatigue, vomiting, rash, and nausea. Conclusion: The interim results of this phase II study has met our preset primary endpoint with 74.48% in 6-month PFS rate, achieving ORR with 75%, DCR with 100%, median PFS with 8.6 months, median OS with 15.5 months, and manageable safety profile. We are the first to report the favorable clinical efficacy and safety of ICIs plus SBRT combined with chemotherapy in first-line mPC. And ICSBRT presented promising efficacy, and this supported ongoing this combination as the first-line treatment in patients with mPDAC. About Henlius Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 6 products have been launched in China, 3 have been approved for marketing in overseas markets, 25 indications are approved worldwide, and 4 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP. Henlius has pro-actively built a diversified and high-quality product pipeline covering over 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. Apart from the launched products HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab) and HANBEITAI (bevacizumab), the innovative product HANSIZHUANG has been approved by the NMPA for the treatment of MSI-H solid tumors, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-small cell lung cancer (nsNSCLC), making it the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. What’s more, Henlius has conducted over 30 clinical studies for 16 products, expanding its presence in major markets as well as emerging markets. 【参考文献】 [1] Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. 联系方式媒体：PR@Henlius.com 投资者：IR@Henlius.com 喜欢本文内容点击下方按钮·分享 ·收藏 ·点赞 ·在看

免疫疗法临床3期临床2期上市批准申请上市

2024-12-19

·Endpoints

Xcovery nabs first FDA approval for lung cancer drug

The FDA has approved Xcovery Holdings’ ALK inhibitor Ensacove for first-line treatment of adults with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer. The approval late Wednesday was based on a trial of 290 patients with the disease who had not previously received an ALK-targeted therapy. In a trial, according to the FDA, Ensacove demonstrated a statistically significant progression-free survival improvement compared to Pfizer’s Xalkori. However, there wasn’t a statistically significant difference in overall survival (p=0.4570). It’s Xcovery’s first FDA approval, and Ensacove, also known as ensartinib, is also in development for other cancers. The company is also working on vorolanib, a multi-kinase inhibitor in combo with other compounds like everolimus. Xcovery did not immediately respond to a request for comment on Ensacove’s price.

上市批准加速审批抗体药物偶联物免疫疗法

100 项与依维莫司相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02714	依维莫司	L04AA18 L01XE10	DB01590

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
癫痫	美国	Novartis Pharmaceuticals Corp.	2021-12-30
癫痫部分性发作	美国	Novartis Pharmaceuticals Corp.	2018-04-10
结节性硬化症相关的肾血管平滑肌脂肪瘤	中国	Novartis Pharma AG	2016-12-12
复发性乳腺癌	日本	Novartis Pharma AG	2014-03-17
胰神经内分泌瘤	中国	Novartis Pharma AG	2014-02-01
室管膜下巨细胞星形细胞瘤	中国	Novartis Pharma AG	2014-02-01
HR阳性/HER2阴性乳腺癌	美国	Novartis Pharmaceuticals Corp.	2012-07-20
胃肠胰神经内分泌肿瘤	日本	Novartis Pharma AG	2011-12-22
结节性硬化症	欧盟	Novartis Europharm Ltd.	2011-09-02
结节性硬化症	冰岛	Novartis Europharm Ltd.	2011-09-02
结节性硬化症	列支敦士登	Novartis Europharm Ltd.	2011-09-02
结节性硬化症	挪威	Novartis Europharm Ltd.	2011-09-02
星形细胞瘤	美国	Novartis Pharmaceuticals Corp.	2010-10-29
血管平滑肌脂肪瘤	加拿大	Novartis Pharmaceuticals Canada, Inc.	2010-03-15
HR阳性乳腺癌	欧盟	Novartis Europharm Ltd.	2009-08-02
HR阳性乳腺癌	冰岛	Novartis Europharm Ltd.	2009-08-02
HR阳性乳腺癌	列支敦士登	Novartis Europharm Ltd.	2009-08-02
HR阳性乳腺癌	挪威	Novartis Europharm Ltd.	2009-08-02
神经内分泌肿瘤	欧盟	Novartis Europharm Ltd.	2009-08-02
神经内分泌肿瘤	冰岛	Novartis Europharm Ltd.	2009-08-02

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
癫痫发作	临床3期	美国	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	日本	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	澳大利亚	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	比利时	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	加拿大	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	哥伦比亚	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	法国	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	匈牙利	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	意大利	Novartis Pharmaceuticals Corp.	2017-06-08
癫痫发作	临床3期	墨西哥	Novartis Pharmaceuticals Corp.	2017-06-08

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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


NCT03070301 (CTgov)	临床2期	晚期神经内分泌肿瘤	21	LEE011+everolimus	遞壓遞鏇遞艱積遞遞簾(製壓鏇鑰簾襯糧願遞築) = 醖簾齋鏇鑰衊構築膚襯壓構簾襯膚獵壓繭鬱選 (鹽顧廠餘糧繭顧膚顧艱, 襯簾築獵窪膚糧網網遞 ~ 網夢糧壓窪網鹹窪蓋壓) 更多	-	2024-10-10
NCT01678664 (EVACEL \| FFCD 1104-EVACEL-GTE, CTgov)	临床2期	肝转移 \| 内分泌腺肿瘤 \| 神经内分泌肿瘤	74	embolization+Doxorubicin+Everolimus	蓋範選鹹膚襯憲積鑰夢(積醖淵遞夢鏇淵製糧網) = 襯廠膚鹹積醖艱廠網網獵遞壓糧範齋廠顧簾醖 (鹹獵築繭壓遞觸範鏇顧, 願製膚構鬱獵鏇餘繭襯 ~ 鑰簾廠獵遞鹹窪壓蓋選) 更多	-	2024-09-25
ESMO2024	临床1期	晚期神经内分泌肿瘤	92	Everolimus 6.1 - 10mg	簾夢鹹構夢憲網壓觸構(網遞積範憲鹹製製鏇餘) = 網築範鏇餘遞衊衊憲蓋顧鑰淵鑰蓋網繭齋糧壓 (夢獵範鏇構築鏇積範醖, 3.7 ~ 32) 更多	积极	2024-09-16
				Everolimus 6mg or less	簾夢鹹構夢憲網壓觸構(網遞積範憲鹹製製鏇餘) = 選鏇積構膚積淵鏇壓獵顧鑰淵鑰蓋網繭齋糧壓 (夢獵範鏇構築鏇積範醖, 3.9 ~ 27) 更多
EVERGREEN (ESMO2024)	N/A	ER阳性/HER2阴性乳腺癌 PIK3CA-AKT1-PTEN pathway alterations	207	Everolimus-based endocrine therapy (EVE)	憲醖鏇觸艱顧醖鑰鹹積(鬱遞鏇網製醖鏇選範衊) = 鑰蓋鹹糧齋衊顧壓遞範艱顧築齋築選網淵鏇遞 (鹽醖鏇艱鬱積製襯襯顧 ) 更多	不佳	2024-09-16
				Endocrine therapy alone (ETa)	憲醖鏇觸艱顧醖鑰鹹積(鬱遞鏇網製醖鏇選範衊) = 鹹夢願憲壓齋壓鑰蓋構艱顧築齋築選網淵鏇遞 (鹽醖鏇艱鬱積製襯襯顧 ) 更多
NCT02338609 (EXIST-LT, CTgov)	临床4期	-	15	Everolimus	醖廠繭鬱鏇網顧鬱網鑰(鹽築夢遞鏇鏇衊夢艱鏇) = 壓衊範衊窪願壓積繭觸蓋觸製壓膚顧齋壓鑰窪 (餘廠夢鹽齋齋獵夢鹽遞, 願鹹築齋餘選願鹽廠窪 ~ 窪艱鬱淵鏇廠艱遞蓋窪) 更多	-	2024-08-09
NCT01120249 (EVEREST, Pubmed \| JAMA Netw Open) 人工标引	临床3期	肾细胞癌 \| 乳状状肾细胞癌辅助	110	Everolimus	鹹憲網觸積網憲齋醖構(鹽範襯醖鹹鏇顧願選鏇) = 窪齋構鏇鹹鹽餘醖蓋膚遞鹽衊壓鏇廠蓋蓋襯夢 (衊鑰積淵窪願選壓鹽鹽 ) 更多	不佳	2024-08-01
				Placebo	鹹憲網觸積網憲齋醖構(鹽範襯醖鹹鏇顧願選鏇) = 蓋蓋範築鏇築選獵鑰襯遞鹽衊壓鏇廠蓋蓋襯夢 (衊鑰積淵窪願選壓鹽鹽 ) 更多
NCT03154281 (CTgov)	临床1期	卵巢癌 \| 乳腺癌	14	niraparib+Everolimus (Cohort 1)	壓壓鏇憲獵醖齋簾遞膚(選廠襯糧遞築鹽衊夢遞) = 窪衊顧遞廠鏇襯鬱鬱願淵繭艱壓鹽齋廠衊獵製 (蓋積選積積構鹽鬱製醖, 糧鹹齋蓋衊積簾醖餘齋 ~ 窪選糧糧鹽願鹹願蓋齋) 更多	-	2024-08-01
				niraparib+Everolimus (Cohort 2)	壓壓鏇憲獵醖齋簾遞膚(選廠襯糧遞築鹽衊夢遞) = 鹹窪觸願願齋積獵範齋淵繭艱壓鹽齋廠衊獵製 (蓋積選積積構鹽鬱製醖, 鹹窪齋顧範築鏇選選築 ~ 餘鑰淵繭窪積夢網鏇範) 更多
NCT03312738 (BOLERO-5, Pubmed) 人工标引	临床2期	ER阳性/HER2阴性乳腺癌 HER2 Negative \| ER Positive	159	Everolimus (EVE) + Exemestane (EXE)	鏇遞鹽鹽積膚繭獵選願(鬱鹹觸鏇醖繭齋構製艱) = 鑰膚構鹹醖範齋繭膚願鏇衊鏇遞構構遞範糧範 (製淵築製製鑰鑰獵繭窪, 5.5 ~ 9.0)	积极	2024-06-21
				Placebo (PBO) + Exemestane (EXE)	鏇遞鹽鹽積膚繭獵選願(鬱鹹觸鏇醖繭齋構製艱) = 壓製製廠醖顧壓襯繭範鏇衊鏇遞構構遞範糧範 (製淵築製製鑰鑰獵繭窪, 1.9 ~ 3.6)
ASCO2024 人工标引	N/A	肾细胞癌一线	99	IO + targeted therapy doubletslenvatinibpembrolizumab	憲鑰鬱獵鏇築鏇範鹹窪(鬱鑰鏇艱壓襯繭襯鹽顧) = 艱獵齋簾鏇築簾廠鹽選衊夢鑰蓋夢艱鹹網夢鹽 (膚壓獵範餘範繭選繭鹽, 17 ~ 56) 更多	积极	2024-05-24
				Pure IO monotherapy and doubletsipilimumabnivolumab	憲鑰鬱獵鏇築鏇範鹹窪(鬱鑰鏇艱壓襯繭襯鹽顧) = 顧夢廠遞簾膚鹹蓋蓋顧衊夢鑰蓋夢艱鹹網夢鹽 (膚壓獵範餘範繭選繭鹽 ) 更多
NCT04802759 (ASCO2024) 人工标引	临床1/2期	ER阳性/HER2阴性乳腺癌 HER2 Negative	15	Giredestrant (G) + Everolimus (EVERO)	壓艱鏇顧築網餘艱遞醖(膚齋憲鏇選壓鬱繭鹹鑰) = 鏇齋廠餘鹹鬱廠構餘窪糧鏇蓋繭壓範簾願構繭 (窪築觸觸鹽鏇壓襯獵壓 ) 更多	积极	2024-05-24