Albumin-Bound Paclitaxel

Phase III NAPOLI 3 trial is the largest and has the longest follow-up for an interventional study in metastatic pancreatic adenocarcinoma1 Post-hoc analysis of NAPOLI 3 study determined characteristics associated with long-term survival, with median overall survival of 19.5 months amongst long-term survivors receiving Onivyde® plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX) regimen as a first-line therapy2 Dose reductions and/or treatment delays for the management of adverse events enabled patients to stay on treatment longer and achieve high cumulative doses of liposomal irinotecan and oxaliplatin2 31 May 2025 – Late-breaking (LBA4175) post-hoc analysis data from the Phase III NAPOLI 3 study were presented today at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. These results found a median overall survival (mOS) of 19.5 months among long-term survivors (n=15) with metastatic pancreatic adenocarcinoma (mPDAC) treated with the Onivyde® (irinotecan liposome injection) plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX) regimen as a first-line treatment (n=120), with younger age at diagnosis, and certain tumor and metastasis locations associated with long-term survivorship.2 Pancreatic adenocarcinoma (PDAC) is the most common type of cancer that forms in the pancreas, with more than 60,000 people diagnosed annually in the U.S. and nearly 500,000 people globally.3,4 It is often detected after the disease has spread to other parts of the body (metastatic or stage IV)5 and fewer than 20% of people diagnosed with metastatic pancreatic adenocarcinoma (mPDAC) survive longer than one year.5,6 Overall, pancreatic cancer has the lowest five-year survival rate of all cancer types globally and in the U.S.5,6 “When people are diagnosed with metastatic pancreatic adenocarcinoma, the most important question remains: how long will they have with their loved ones,” said Dr. Vincent Chung, Medical Oncologist, City of Hope. “Findings from the NAPOLI 3 post-hoc analysis provide important context on long-term overall survival with the Onivyde (NALIRIFOX) treatment regimen.” The analysis included patients who survived for 18 months or longer (N=15), with findings showing long-term survivors living with mPDAC had a mOS of 19.5 months (interquartile range [IQR]: 18.8–22.6).2 Clinical and pathological factors of long-term survivors included younger than average age at time of diagnosis (median age 61.0 (IQR: 49.0–70.5) as well as tumor location.2 Fewer patients had tumors in the head or tail of the pancreas (53.3% had the main pancreatic tumor located in the body of the pancreas), a substantial proportion had liver metastasis (66.7%) and ≥3 metastatic sites (53.3%).2 Additionally, findings indicate dose reduction and treatment delays resulted in prolonged exposure and higher cumulative doses of the Onivyde (NALIRIFOX) regimen.1 Liver metastasis and ≥3 metastatic sites, dose modifications and an otherwise good clinical profile enabled people to achieve a long mOS.2 Consideration should be taken when interpreting these results as a post-hoc analysis with a small sample size. "Data from the Phase III NAPOLI 3 trial were the first positive data of its kind in a decade and continue to reinforce the potential for long-term outcomes with the Onviyde (NALIRIFOX) regimen,” said Sandra Silvestri, MD, PhD, Executive Vice President, Chief Medical Officer, Ipsen. “With people on average living just 4-6 months following diagnosis with pancreatic adenocarcinoma, these data help us to understand the characteristics associated with long-term survival seen in the NAPOLI trial, an important advancement for this difficult-to-treat cancer where data of this kind are scarce.” Onivyde is a long-circulating liposomal topoisomerase inhibitor. In Onivyde, irinotecan is enclosed in tiny fat particles called liposomes which accumulate in the tumor and release slowly over time. Onivyde is administered via intravenous infusion over 90 minutes every two weeks with recommendations on dosing modifications. Onivyde, as part of the NALIRIFOX regimen (combined with oxaliplatin, fluorouracil (FU) and leucovorin (LV)), is for people living with mPDAC who are treatment naïve or used in combination with FU and LV following gemcitabine-based therapy. Onivyde is not indicated as a single agent for the treatment of adult patients with metastatic pancreatic adenocarcinoma. Ipsen has exclusive commercialization rights for the current and potential future indications for Onivyde in the U.S. Servier, an independent international pharmaceutical company governed by a foundation and with an international presence in 140 countries, is responsible for the commercialization of Onivyde outside of the U.S., Taiwan and Canada. PharmaEngine is a commercial stage oncology company headquartered in Taipei and is responsible for the commercialization of Onivyde in Taiwan. NAPOLI 3 is a randomized, open-label Phase III trial of an Onivyde treatment regimen (NALIRIFOX) in treatment-naïve mPDAC. NAPOLI 3 enrolled 770 patients across 187 trial site locations in 18 countries across Europe, North America, South America, Asia, and Australia. Patients were randomized to receive Onivyde plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX regimen; n=383) twice in a month (days 1 and 15 of 28-day cycle) compared to an injection of nab-paclitaxel and gemcitabine (n=387) administered three times a month (days 1, 8, 15 of a 28-day cycle). We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries. References 1 Wainberg et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023 Oct 7;402(10409):1272-1281. 2 Chung et al. NAPOLI 3 phase 3 study of NALIRIFOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): final overall survival (OS) analysis and characteristics of the long-term survivors. As presented at ASCO Congress 2025 Chicago, USA 3 American Cancer Society – Cancer Facts and Figures 2024. Available : https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf 4 https://www.cancer.net/cancer-types/pancreatic-cancer/statistics 5 Orth, M., Metzger, P., Gerum, S. et al. Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiat Oncol 14, 141 (2019). https://doi.org/10.1186/s13014-019-1345-6 The content above comes from the network. if any infringement, please contact us to modify.

截至 2025 年 4 月，FDA 已批准了 14 种检查点抑制剂，例如我们熟知的默沙东重磅 PD-1 抑制剂 Keytruda已成为拥有 40 多种癌症适应症疗法，包括各种形式的肺癌和妇科癌症等。该药连续位居制药公司最畅销产品榜首。2024 年，Keytruda 同比增长18%，销售额达到 294.8 亿美元。 面对如此巨大的成功，制药公司纷纷投入到免疫检查点抑制剂研究中。然而，有成功必然有失败，本文盘点了一些免疫检查点抑制剂的失败与成功案例，由此可以看出免疫检查点抑制剂领域的研发趋势。失败案例：TIGIT2021 年 12 月，FDA授予罗氏TIGIT靶点新型癌症免疫疗法Tiragolumab突破性治疗药物（BTD），联合抗PD-L1疗法Tecentriq（泰圣奇），一线治疗肿瘤呈现PD-L1高表达、无EGFR或ALK基因组肿瘤畸变的转移性非小细胞肺癌（NSCLC）患者。虽然II 期临床试验结果令人鼓舞但这种情况并没有持续下去。2024年，在一项 II/III 期研究中，与 Keytruda 和化疗相比，该联合疗法未能显著改善 NSCLC 的无进展生存期和总生存期。同年5月，Tiragolumab单抗与Atezolizumab联用一线治疗PD-L1高表达局部晚期或转移性NSCLC III期SKYSCRAPER-01研究，未达到其无进展生存期（PFS）的主要终点。7月，Tiragolumab+Atezolizumab+化疗用于一线治疗NSCLC的III期临床研究SKYSCRAPER-06没有达到无进展生存期（PFS）和总生存期（OS）的主要终点，Tiragolumab成为全球首个TIGIT III期临床失败案例。在此之前，默沙东也传出了同样令人失望的消息，。2023年3月，II期KeyVibe-002研究表明Vibostolimab与PD-1联用治疗NSCLC的中治疗效果不如多西他赛；2024年5月，因为免疫副作用，默沙东停止了Vibostolimab联用K药辅助治疗黑色素瘤的III期临床；8月，默沙东再次终止了Vibostolimab联用K药用于一线治疗小细胞肺癌的III期临床；12月，默沙东不得不遗憾地终止Vibostolimab临床研究。该领域的其他参与者包括百济神州、阿斯利康、吉利德和 Arcus Biosciences等也同样命途多舛，至今未能成药。究其原因，可能是TIGIT靶点在肿瘤免疫调节中的作用从一开始就被高估了，也可能TIGIT参与的免疫调节机制十分复杂，与其他免疫检查点以及免疫细胞之间存在着错综复杂的相互作用。也可能是由于联合用药用药顺序、剂量、治疗周期等因素还有优化空间。2024年 9 月，iTeos Therapeutics 的抗 TIGIT belrestotug 与 GSK 的抗 PD-1 疗法Jemperli 联合治疗，在 NSCLC 的确认客观缓解率方面优于 Jemperli 单药治疗 30%，这一结果让研发人员看到了TIGIT靶点的新希望。成功案例：PD-1/VEGF双抗TIGIT靶点固然有其局限性，但让制药巨头纷纷终止临床试验的另一个原因或许还有双抗的崛起。依达方®（依沃西单抗康）是康方生物自主研发的、全球首创PD-1/VEGF双特异性肿瘤免疫治疗药物。2024年5月获得中国国家药品监督管理局批准上市，联合化疗用于经表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗进展的EGFR突变的局部晚期或转移性非鳞非小细胞肺癌（nsq-NSCLC）。此外，依达方®单药一线治疗PD-L1表达阳性的晚期NSCLC的新药上市申请（sNDA）已获受理并被纳入优先审评品种名单，有望成为肺癌一线“去化疗”治疗的新标准方案。该sNDA是基于AK112-303 / HARMONi-2试验，该研究表明，依达方®是全球迄今唯一在单药头对头III期临床研究中证明疗效显著优于“药王”帕博利珠单抗的药物。依达方®已通过单药和联合用药，在包括肺癌、头颈鳞癌、胆道癌、胰腺癌、乳腺癌、肝细胞癌、结直肠癌等17个适应症领域布局。BioNTech 也是该领域的竞争者，2024 年 11 月， BioNTech斥资9.5亿美元收购合作伙伴中国创新药企普米斯生物后获得了 PD-L1/VEGF-A 双特异性抗体 BNT327/PM8002 的全部权利。BioNTech将先支付8亿美元，并可能在开发和商业里程碑达成后支付额外的1.5亿美元。在2024年美国圣安东尼奥乳腺癌学术会议（SABCS）上， 1b/2期研究的结果表明PM8002/BNT327联合白蛋白结合型紫杉醇（Abraxane），治疗转移性三阴性乳腺癌（TNBC），取得了非常显著的疗效。BNT327/PM8002联合化疗在 EGFR-TKI 治疗后进展的 EGFR 突变 NSCLC 患者中也显示出令人鼓舞的抗肿瘤活性和可接受的耐受性。2025年5月20日，辉瑞公司投入了高达 12.5 亿美元的前期资金，与三生合作开发 PD-1/VEGF 双特异性抗体。该交易还包括高达 48 亿美元的可能里程碑，以及 SSGJ-707 药物上市后的销售特许权使用费。SSGJ-707是三生制药开发的靶向PD-1/VEGF双特异性抗体，可同时抑制PD-1和VEGF双靶点。II期临床阶段性分析数据显示，SSGJ-707在非小细胞肺癌（NSCLC）患者的治疗上获得了优异的客观缓解率（ORR）和疾病控制率（DCR），无论单药还是与化疗联用，均展示出显著的抗肿瘤活性和良好的安全性，具有best-in-class（同类最优）的潜力。4月17日，SSGJ-707获中国药监局突破性治疗药物认定，适应症为一线治疗PD-L1表达阳性的局部晚期或转移性非小细胞肺癌（NSCLC）。而除非小细胞肺癌外，SSGJ-707用于治疗结直肠癌、妇科肿瘤等领域的临床研究也在推进中。值得注意的是康方、普米斯生物、三生都是中国制药公司，他们在PD-1/VEGF双特异性抗体领域的研发已走在了世界前列，因此，西方制药巨头转向中国寻求创新、突破。尽管面临监管障碍和地缘政治紧张等挑战，中国生物技术领域已成为突破性药物开发的热点，吸引了全球关注。总结：免疫检查点抑制剂作为一种革命性的免疫疗法药物，通过阻断免疫系统中的关键通路，增强机体对癌细胞的攻击能力。 这类药物主要针对关键性免疫检查点分子，通过激活患者的免疫反应来有效抗击癌症。然而，此类药物机制比较复杂，免疫检查点分子种类也较多，找到合适的靶点、或联用靶点去开发新的药物存在挑战，且在FDA 已批准检查点抑制剂中，患者对对此类免疫疗法的反应率也只有30% 左右。高效精准的靶点筛选平台或许可以提高免疫检查点抑制剂研发的成功率。期待更多的突破性免疫检查点抑制剂药物可以上市，早日造福患者。药事纵横投稿须知：稿费已上调，欢迎投稿