Durvalumab

HONG KONG, Sept. 2, 2025 /PRNewswire/ -- Akeso (9926.HK) has recently announced the completion of patient enrollment in its Phase III, multicenter, randomized, controlled, registrational study evaluating ivonescimab, in combination with standard therapy, against durvalumab (PD-L1) combination therapy, for the first-line treatment of advanced biliary tract cancer (BTC) (AK112-309/HARMONi-GI1). This Phase III trial is being conducted in China. Ivonescimab has previously shown significant positive results in the randomized, double-blind, controlled Phase III study (HARMONi-2), where it was compared head-to-head with pembrolizumab. These results led to its approval as a first-line treatment for PD-L1-positive non-small cell lung cancer (NSCLC), marking its second approved indication. In addition, the Phase III trial of ivonescimab in combination with chemotherapy compared to tislelizumab combined with chemotherapy as a first-line treatment for squamous NSCLC, also delivered significant positive outcomes. These results highlight ivonescimab's strong clinical breakthroughs. Whether compared to PD-1 monotherapy, PD-1 plus chemotherapy (current standard therapies for various cancers), or VEGF-related treatments, ivonescimab has consistently demonstrated its ability to drive clinical innovation. Ivonescimab continues to validate its clinically meaningful profile and potential with a strategically expanded development program targeting key immuno-oncology settings: Phase III trials for Lung cancer (8 registrational/Phase III trials, 4 already met primary endpoints): First-line NSCLC, squamous and non-squamous (versus pembrolizumab + chemotherapy; global trial) First-line squamous NSCLC (versus tislelizumab + chemotherapy) NSCLC after progression on EGFR-TKI therapy (HARMONi-A and HARMONi studies) First-line PD-L1-positive NSCLC (versus pembrolizumab monotherapy) First-line PD-L1-high expressing NSCLC (versus pembrolizumab) IO-resistant NSCLC Consolidation therapy for limited-stage small cell lung cancer (LS-SCLC) without progression after concurrent chemoradiotherapy (cCRT) Phase III trials for core immuno-oncology indications (first-line therapy ): First-line biliary tract cancer (versus durvalumab + chemotherapy) First-line PD-L1-positive head and neck squamous cell carcinoma (HNSCC) in combination with ligufalimab (anti-CD47) versus pembrolizumab Phase III trials for cold tumors and more: First-line triple-negative breast cancer (TNBC) First-line MSS/pMMR colorectal cancer (representing about 95% of CRC cases) First-line pancreatic cancer Additional global Phase III trials are in advanced stages of planning An extensive clinical foundation includes over 20 Phase II studies across more than 10 additional tumor types, generating compelling efficacy and safety data that enable rapid transition to further registrational studies worldwide. Ivonescimab uniquely targets both PD-1 and VEGF, producing a synergistic anti-tumor effect. This dual mechanism not only combines the benefits of PD-1 and VEGF inhibition but also overcomes the efficacy and safety limitations of each target alone, resulting in pronounced clinical benefits. These advantages have been confirmed across multiple Phase III trials and real-world use, rapidly establishing ivonescimab as a next-generation leader in immunotherapy and anti-angiogenic therapy. For context, pembrolizumab (anti-PD-1) is approved for over 40 oncology indications, and bevacizumab (anti-VEGF) for more than 10. Akeso is implementing a dual-path strategy to maximize the value of ivonescimab worldwide: accelerating domestic commercialization and label expansion in China, while simultaneously advancing global development in partnership with Summit Therapeutics. Forward-Looking Statement of Akeso, Inc. This announcement by Akeso, Inc. (9926.HK, "Akeso") contains "forward-looking statements". These statements reflect the current beliefs and expectations of Akeso's management and are subject to significant risks and uncertainties. These statements are not intended to form the basis of any investment decision or any decision to purchase securities of Akeso. There can be no assurance that the drug candidate(s) indicated in this announcement or Akeso's other pipeline candidates will obtain the required regulatory approvals or achieve commercial success. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in P.R.China, the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Akeso's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Akeso's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. Akeso does not undertake any obligation to publicly revise these forward-looking statements to reflect events or circumstances after the date hereof, except as required by law. About Akeso Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research, development, manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012, the company has created a unique integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the core, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode, and has gradually developed into a globally competitive biopharmaceutical company focused on innovative solutions. With fully integrated multi-functional platform, Akeso is internally working on a robust pipeline of over 50 innovative assets in the fields of cancer, autoimmune disease, inflammation, metabolic disease and other major diseases. Among them, 24 candidates have entered clinical trials (including 15 bispecific/multispecific antibodies and bispecific ADCs. Additionally, 7 new drugs are commercially available. Through efficient and breakthrough R&D innovation, Akeso always integrates superior global resources, develops the first-in-class and best-in-class new drugs, provides affordable therapeutic antibodies for patients worldwide, and continuously creates more commercial and social values to become a global leading biopharmaceutical enterprise. For more information, please visit and follow us on Linkedin. SOURCE Akeso, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

点击蓝字 关注我们 本 期 看 点 恶性胆道系统肿瘤（Biliary tract carcinoma，BTC）较为少见，但诊断和治疗较为棘手，有着“小癌王”之称。既往系统治疗主要以化疗为主，随着TOPAZ-1、KeyNote966两项全球大III期获得阳性结果，免疫联合化疗成为BTC系统治疗的新一线标准。康方生物的依沃西单抗（AK112，PD-1/VEGF双抗）于2024年8月开展头对头度伐利尤单抗+化疗的随机III期研究。2025年9月2日宣布完成入组，速度可谓是快。这是继依沃西单抗联合化疗对比帕博利珠单抗联合化疗一线治疗转移性鳞状非小细胞肺癌的随机3期研究后再次硬刚MNC旗下重磅ICIs，足见康方生物对于依沃西单抗的信心十足。 本期内容 01 依沃西单抗丨BTC一线丨三期 02 依沃西单抗丨BTC一线丨Ib/II期 03 II期数据同比，是否仍具优势？ 04 总结与展望 【01 依沃西单抗丨BTC一线丨三期】 日前，康方生物（9926.HK）独立自主研发的PD-1/VEGF双特异性抗体依沃西联合方案，对比度伐利尤单抗（PD-L1）联合方案，用于一线治疗晚期胆道恶性肿瘤（BTC）的随机、对照、多中心、注册性III期临床研究（AK112-309/HARMONi-GI1）完成患者入组。 康方生物的依沃西单抗（AK112，PD-1/VEGF双抗）在肝胆领域动作频繁，先后在肝癌领域尝试双抗联双抗和双抗联合靶向加介入的注册研究：康方PD-1/CTLA-4双抗+PD-1/VEGF双抗，“剑指”HCC、康方双抗开展肝癌三期，靶+免+介入三联疗法重塑HCC治疗格局。而在已经有TOPAZ-1、KeyNote966两项全球大III期验证成功的晚期胆道肿瘤（BTC）一线，2024年8月25日，康方生物开展了依沃西单抗（AK112）联合化疗对比度伐利尤单抗联合化疗一线治疗晚期胆道癌的头对头III期临床试验，主要研究者为哈尔滨医科大学附属肿瘤医院的郑桐森教授和复旦大学附属中山医院的周俭教授。共计入组患者人数为682例。 cited by：药物临床试验登记与信息公示平台 该项研究的开启，也即意味着继依沃西单抗（AK112，PD-1/VEGF双抗）联合化疗对比帕博利珠单抗联合化疗一线治疗转移性鳞状非小细胞肺癌的随机3期研究后，依沃西单抗再次挑战MNC的重磅ICIs，此次BTC领域正面硬刚阿斯利康的度伐利尤单抗，足见康方生物对于依沃西单抗的信心十足。 cited by：药物临床试验登记与信息公示平台 2024年ASCO大会中，浙江省肿瘤医院应杰儿团队牵头的，采用康方生物自主研发的依沃西单抗（PD-1/VEGF双抗）联合标准化疗一线治疗胆道恶性肿瘤（BTC）的研究，整体疗效数据较为优异，尤其是胆囊癌患者。 02 依沃西单抗丨BTC一线丨Ib/II期 NCT05214482是一项开放、多中心、Ib/II期研究，旨在探讨依沃西单抗（PD-1/VEGF双抗）联合化疗±AK117(CD47单抗) 的安全性和有效性。本次报告中，该研究共入组22例BTC患者，均采用依沃西单抗联合吉西他滨和顺铂治疗，中位随访时间13.8个月，疗效和安全性如下： ≥3级TRAE占86.4%，但无治疗导致的停药或死亡。 ORR达63.6%(14/22)，DCR为100%。 mPFS达8.5个月(95%CI, 6.8-10.5)，mOS达16.8个月(95%CI, 9.2-NE)。 在既往的Keynote-966研究中，第一次中期分析时，中位随访时间13.6个月，帕博利珠单抗联合化疗组的mPFS为6.5个月(95%CI, 5.7-6.9)，ORR为29%。而在最终分析时 ，mOS报出为12.7个月(95%CI, 11.5-13.8)。       在TOPAZ-1研究中，中位随访时间16.8个月时，度伐利尤联合化疗组的mOS为12.8个月(95%CI, 11.1-14.0)，mPFS达7.2个月(95%CI, 6.7-17.4)，ORR为26.7%。      综上数据，我们粗看无论是ORR，还是PFS和OS，似乎依沃西单抗都极具潜力。但这是II期小样本研究数据，即使我们尽量对比相近的随访时间数据，和大III期研究的数据非头对头比较的可参考性也极其有限。 03 II期数据同比，是否仍具优势？ 事实上，在TOPAZ-1开展前，阿斯利康也曾发布过II期探索结果，NCT03046862研究评估了化疗联合度伐利尤±曲美木单抗在BTC 1L治疗中的安全性和有效性，该研究中度伐利尤单抗联合吉西他滨和顺铂的治疗组共纳入45例患者，中位随访时间11.3个月，疗效数据如下： ORR高达73.4%(60.5-86.3)，DCR为100%。 mPFS为11.0个月(95%CI, 7.0-15.0)，mOS为18.1个月(95%CI, 11.3-24.9)。 该研究单从数值上比较，丝毫不逊于依沃西单抗当前的II期数据。当然，该研究的入组人群为韩国人，且仅为单中心研究，从基线看患者ECOG评分为0的占比也更高。 除此之外，国内一项单中心研究（ChiCTR2100044476）报告了多个PD-1单抗联合仑伐替尼治疗初始不可切除BTC的数据，该研究共纳入38例患者，ORR仅42.1%，DCR为76.3%，由此可见，既往PD-1单抗联合或不联合抗血管靶向药在BTC 1L治疗的II期数据差异极大，可参考程度也很有限。那么，基于依沃西单抗本次报道的数据自身比较，是否能客观的看出一些信号呢？ 依沃西单抗亚组分析，胆囊癌优势明显 从Keynote-966和TOPAZ-1的亚组分析中，我们可以明确看到，免疫治疗的加入主要对肝内胆管癌起到作用，而在肝外胆管癌和胆囊癌中并无明显获益优势。 但本次康方报出的依沃西单抗研究中，专门提到胆囊癌亚组，ORR高达77.8%，mOS为16.8个月。 虽然当前入组数量较少，但是否该信号提示，PD-1/VEGF双抗有望在此类人群中有重要突破？这一特点是否和康方另一款已上市双抗——卡度尼利单抗（PD-1/CTLA-4双抗）有异曲同工？前期无论卡度尼利单抗在宫颈癌适应症中数据，还是2024AACR最新报出的胃癌III期数据，均显示其无论PD-L1的表达，可全人群获益，这相较于既往的PD-1单抗而言，PD-L1低表达人群仍可显著获益是一大亮点。那么如今依沃西单抗是否也能凭借其独有的双抗结构优势，为既往单免不能获益的人群带来新的希望呢？该优势究竟来源于靶免联合的协同作用特点，还是双抗独特的结构作用，更多分析我们拭目以待。 04 总结与展望 随着依沃西在越来越多肿瘤适应症迭代PD-1疗法或VEGF疗法的推进，依沃西的全球市场潜力也越发凸显。 参考文献1. Annals of Oncology (2024) 35 (suppl_1): S119-S161. 10.1016/annonc/annonc14812                                                                                                                                                . Jieer Ying, et al. 2024 ASCO, poster4095.3. Kelley RK, et al. Lancet. 2023, 401(10391):1853-1865. 4. Oh DY, et al. NEJM Evid. 2022, 1(8):EVIDoa2200015. 5. Oh DY, et al. Lancet Gastroenterol Hepatol. 2022, 7(6):522-532. 6. Zhang Q, et al. Front Oncol. 2021, 11:751391. 行文不易，欢迎关注，为中国的Biotech行业保驾护航，也是人生幸事。 科普新号，用浅显易懂的语言，惠及广泛人群。 ★