Durvalumab

HONG KONG , Nov. 5, 2026 /PRNewswire/ -- Akeso, Inc. (9926.HK) today announced that results from a Phase II clinical study evaluating its first-in-class PD-1/VEGF bispecific antibody ivonescimab in the perioperative treatment of resectable non-small cell lung cancer (NSCLC) have been published in the journal Nature Medicine . This Phase II trial assessed the efficacy and safety of perioperative ivonescimab administered either as monotherapy or in combination with chemotherapy. Patients received neoadjuvant treatment followed by surgical resection and subsequent adjuvant ivonescimab. The study demonstrated that neoadjuvant ivonescimab in combination with chemotherapy produced high rates of pathological response in patients with resectable NSCLC. Among patients who underwent surgery, the major pathological response (MPR) rate was 70.1% and the pathological complete response (pCR) rate was 50.7%. Key findings: In the ivonescimab plus chemotherapy cohort, the MPR rate reached 70.1%, the pCR rate was 50.7%, and 68.7% of patients had residual viable tumor (RVT) ≤5%. The ivonescimab monotherapy cohort also showed meaningful pathological responses, with an MPR rate of 60.0% and a pCR rate of 30.0%. Both cohorts achieved high objective response rates and frequent T-stage downstaging. All patients who proceeded to surgery achieved R0 resection (100%). The 12-month event-free survival (EFS) rates exceeded 80% in both arms, comparing favorably with outcomes reported in prior Phase III perioperative immunotherapy trials. Subgroup analyses revealed particularly notable activity in clinically relevant populations: patients with squamous histology achieved an MPR rate of 81.5% and a pCR rate of 61.1%; those with Stage III disease achieved an MPR rate of 65.5% and a pCR rate of 47.3%; and PD-L1-negative patients achieved an MPR rate of 69.2%, comparable to that observed in PD-L1-positive patients. The perioperative safety pro ivonescimab was manageable. No grade ≥3 bleeding events occurred, and no surgeries were cancelled due to treatment-related adverse events. Approximately one-quarter of patients with NSCLC have resectable disease at the time of diagnosis. Nevertheless, 30–70% of patients experience disease recurrence after surgery, frequently with distant metastases, contributing to poor long-term outcomes. Although neoadjuvant immuno-chemotherapy is now established in treatment guidelines, current regimens leave room for improvement, particularly in subgroups such as Stage IIIB disease, squamous histology, and PD-L1-negative tumors, where unmet clinical need remains substantial. These Phase II results further support the potentially important role of ivonescimab as a next-generation immunotherapy option across the continuum of NSCLC treatment options. About Ivonescimab Ivonescimab is a first-in-class PD-1/VEGF bispecific antibody independently developed by Akeso. It is the world's first approved bispecific antibody that combines immuno-oncology and anti-angiogenesis mechanisms in a single molecule, helping to define a new generation of bispecific immuno-oncology therapies. Ivonescimab is also the first therapy to demonstrate positive results in a Phase III head-to-head study against pembrolizumab. Building on its strong clinical pro the IO2.0 landscape, Akeso is advancing a comprehensive global development program for ivonescimab across multiple tumor types and treatment settings. As a cornerstone of the Company's IO2.0 + ADC2.0 strategy, ivonescimab aims to help reshape standards of care in major cancers worldwide. More than 17 Phase III studies of ivonescimab are underway globally, including seven international multi-regional registrational Phase III trials and seven head-to-head studies versus PD-1/PD-L1 therapies. These programs encompass eight registrational or Phase III studies in lung cancer, as well as trials in first-line MSS/pMMR colorectal cancer, first-line PD-L1-positive head and neck squamous cell carcinoma (in combination with ligufalimab versus pembrolizumab), first-line biliary tract cancer (versus pembrolizumab/ durvalumab-based regimen), first-line triple-negative breast cancer, first-line pancreatic cancer, and first-line urothelial carcinoma (versus pembrolizumab plus a Nectin-4 ADC). Akeso has out-licensed the exclusive rights to develop and commercialize ivonescimab in the United States and Canada, South America, Europe, the Middle East, Africa, and Japan to Summit Therapeutics under an agreement with a total potential value of up to US$5 billion. 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, Akeso has built a comprehensive R&D innovation ecosystem anchored by its proprietary Tetrabody antibody technology platform, AI-powered drug R&D platform, Dual-Shield ADC technology platform, Dual-Lock T-cell engager (TCE) technology platform, Tissue-Smart siRNA/mRNA technology platform, and cell therapy technology platforms. Backed by world-class GMP manufacturing facilities and a highly efficient, integrated commercialization system, Akeso has developed into a globally competitive biopharmaceutical enterprise. Leveraging its fully integrated, multi-functional platform, the Company maintains a robust pipeline of more than 50 innovative assets targeting cancer, autoimmune diseases, inflammation, metabolic disorders, and other major therapeutic areas. Of these, nearly 30 candidates have advanced into clinical trials, including 15 bispecific or multi-specific antibodies and bispecific ADCs. Eight innovative drugs are commercially available, and two additional drugs with three indications are currently under regulatory review for marketing approval. Akeso is committed to becoming a global leader in biopharmaceuticals through efficient and breakthrough innovation in R&D, developing novel therapies that are first-in-class or best-in-class, and providing better disease solutions for patients around the world. Forward-Looking Statements 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 the 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 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. View original content to download multimedia: SOURCE Akeso, Inc.

导读 广泛期小细胞肺癌（ES-SCLC）具有高度侵袭性及快速进展的生物学特征。目前，一线采用化免联合治疗的患者，其中位总生存期（OS）仍局限在12-13个月[1]；而在完成诱导治疗后，单用PD-L1抑制剂进行维持治疗的临床获益较为有限。因此，在疾病获得初步控制的关键窗口期，亟需探索更具协同效应的强化治疗策略，以进一步延长生存期并改善长期预后。塔拉妥单抗作为靶向DLL3/CD3的双特异性T细胞衔接器（TCE）可桥接T细胞与肿瘤细胞，激活内源性T细胞应答，开创SCLC“定向免疫”新范式[2]。 2026年10月23日-27日，欧洲肿瘤内科学会（ESMO）年会在西班牙马德里召开。本次ESMO大会公布的DeLLphi-305研究首次以III期证据确证塔拉妥单抗联合度伐利尤单抗一线维持治疗的生存获益[3,4]。本期「TCE TALK」特邀上海市胸科医院储天晴教授与美国丹娜-法伯癌症研究院Jacob Sands教授，围绕DeLLphi-305研究主要分析、“TCE+免疫”安全性管理及未来探索方向展开解读。 TCE 跃阶 DeLLphi-305 III期研究确证塔拉妥单抗一线维持生存获益 储天晴教授 DeLLphi-305是全球首个在ES-SCLC一线维持阶段评估TCE联合PD-L1单抗的III期研究，本次大会公布的疗效数据达到主要终点。请问该结果对“诱导后强化维持”策略的确证性价值应如何解读？ Jacob Sands教授 DeLLphi-305研究是基于DeLLphi-303研究1b阶段数据结果得以展开。DeLLphi-303研究评估了完成化免联合诱导治疗患者，接受塔拉妥单抗联合阿替利珠单抗或度伐利尤单抗维持治疗的疗效及安全性；2024年WCLC公布的初步数据显示，维持治疗队列中位OS达25.3个月[5]。本届ESMO大会的更新数据显示，中位OS进一步延长至37.9个月（中位随访30.8个月），24个月OS率达58.1%，提示该联合维持模式具有突出的长期生存获益[6]。 DeLLphi-305为全球多中心、随机、开放标签III期研究，纳入完成4周期度伐利尤单抗联合化疗诱导治疗后未出现疾病进展的患者，按1:1随机分配接受度伐利尤单抗联合或不联合塔拉妥单抗维持治疗。结果显示，相较于度伐利尤单抗组，塔拉妥单抗+度伐利尤单抗组患者中位无进展生存期（PFS）由1.9个月延长至7.4个月（HR=0.34，95%CI：0.28-0.42，P<0.001），疾病进展或死亡风险降低66%；中位OS由12.7个月延长至21.1个月（HR=0.42，95%CI：0.32-0.54，P<0.001），死亡风险降低58%。缓解深度方面，塔拉妥单抗+度伐利尤单抗组确认客观缓解率（cORR）为26.4%，度伐利尤单抗组为4.1%（P<0.001），中位缓解持续时间（DOR）分别为12.7个月和5.6个月[3,4]。 图1,2 DeLLphi-305研究患者OS、PFS数据（左右滑动） 储天晴教授 DeLLphi-305研究为TCE在ES-SCLC一线维持治疗中的应用提供了最高等级的循证依据。在诱导化免治疗实现疾病控制的基础上，塔拉妥单抗联合维持治疗较PD-L1单药维持带来明确的生存获益，表明TCE不仅可用于疾病进展后的挽救治疗，亦可在疾病控制窗口期积极介入，有望重塑ES-SCLC一线治疗格局。 TCE 维稳 DeLLphi-305验证“TCE+免疫”维持模式安全可控 Jacob Sands教授 DeLLphi-305研究显示该联合方案安全性可控，TCE联合PD-L1抑制剂的维持治疗模式对ES-SCLC一线治疗格局有何影响？ 储天晴教授 首先，该联合方案的安全性特征与各组分已知特征一致，转入维持治疗后未出现新的安全性信号，且临床已积累较为丰富的管理经验，支持长期维持治疗。其次，主要不良事件集中于治疗早期，以细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）为主：≥3级CRS发生率低，且未观察到≥3级ICANS；随治疗周期推进，不良事件发生率显著下降，长期用药的安全性负担较轻。此外，因不良事件导致的治疗中断及停药率均较低，良好的治疗依从性为长期维持治疗提供了保障[3,4]。 Jacob Sands教授 DeLLphi-305研究中CRS和ICANS的发生率低于既往研究。CRS发生率为50%，其中≥2级仅占8%；≥2级CRS患者中约半数需托珠单抗治疗，1.4%需低流量吸氧。ICANS仅3例（1.1%），无≥3级事件[3,4]。该研究前两次给药后现场观察时间为1-2小时，欧洲部分地区为6-8小时，短于既往研究要求的住院观察时间，整体毒性呈降低趋势。 储天晴教授 疗效与安全性数据共同表明，塔拉妥单抗联合PD-L1抑制剂一线维持治疗模式为ES-SCLC患者提供了高效且可耐受的治疗新选择。 TCE 拓疆 多维度探索未来方向，ES-SCLC全程管理前景光明 储天晴教授 在抗体偶联药物（ADC）、双抗及其他TCE等多类药物研发并进的背景下，塔拉妥单抗的差异化定位及后续重点探索方向是什么？ Jacob Sands教授 在诱导治疗阶段，DeLLphi-312研究评估了塔拉妥单抗联合化疗与度伐利尤单抗的疗效与安全性，该研究塔拉妥单抗自第2周期起开始给药。目前该研究已完成受试者入组，未来结果值得期待。需要注意的是，诱导治疗前入组人群与诱导治疗后入组人群存在差异，早期进展及诱导治疗期间血细胞计数或功能状态下降的患者往往无法进入维持治疗，因此DeLLphi-312纳入的人群更贴近真实临床。DeLLphi-305与DeLLphi-312两项研究均允许纳入无症状且未经治疗的脑转移患者，旨在探索塔拉妥单抗早期干预对疗效的潜在增益。该假设有待DeLLphi-312研究的最终疗效数据予以验证。在局限期小细胞肺癌（LS-SCLC）领域，DeLLphi-306研究评估了同步放化疗后塔拉妥单抗单药巩固治疗相较于安慰剂的临床获益，该研究未采用联合度伐利尤单抗的治疗方案。鉴于ADRIATIC研究已确证度伐利尤单抗在此治疗场景中的显著生存获益，DeLLphi-306研究结果公布后，临床医生将面临如何为患者选定巩固治疗方案的难题。美国协作组正在开展放化疗后度伐利尤单抗联合塔拉妥单抗的研究，有望回答二者联合用于LS-SCLC的价值，其前景值得期待。在生物标志物层面，DeLLphi-305数据公布时间较短，相关探索刚刚起步，目前正围绕组织样本DLL3表达、分子亚型及其他生物标志物展开分析，以指导精准的患者分层。 储天晴教授 DeLLphi-305研究为TCE从二线治疗迈向一线维持治疗奠定了关键基础，是优化ES-SCLC全程管理的重要一步。随着诱导期联合、局限期拓展及生物标志物分层等方向的持续推进，塔拉妥单抗有望进一步改善ES-SCLC患者的生存获益。 总结 DeLLphi-305是SCLC领域首个在一线维持阶段评估TCE联合PD-L1抑制剂的Ⅲ期临床研究，其结果证实塔拉妥单抗联合度伐利尤单抗维持治疗可显著延长患者的PFS与OS，且安全性可控、治疗依从性良好，为ES-SCLC一线维持治疗提供了最高等级的循证依据。该研究确立了“诱导化免后强化维持”的全新治疗范式，推动TCE由疾病进展后的挽救治疗前移至疾病控制窗口期的主动干预，实现了ES-SCLC治疗策略的关键跃升。随着DeLLphi-312等诱导期联合研究、局限期拓展及生物标志物分层探索的持续推进，以塔拉妥单抗为代表的TCE有望进一步重塑ES-SCLC全程管理格局，为患者带来更持久的生存获益。 专家简介 储天晴 教授 上海交通大学医学院附属胸科医院临床研究中心主任 上海交通大学医学院附属胸科医院呼吸内科，主任医师 中国临床肿瘤学会（CSCO）抗血管靶向专业委员会主任委员 中国初级卫生保健基金会胸部肿瘤精准治疗专业委员会主任委员 中国初级卫生保健基金会肿瘤临床转化研究委员会副主任委员 中华医学会中华肺癌学院执行秘书长 中国抗癌协会肿瘤精准治疗专业委员会常委 中国临床肿瘤学会（CSCO）老年肿瘤防治专业委员会常委 中国医药教育协会肿瘤转移专业委员会常委 中国初级卫生保健基金会肺部肿瘤慢性病专委会常委 中国抗癌协会整合肿瘤专委会肺癌学组副组长 中国抗癌协会肿瘤多学科诊疗专委会委员 中国抗癌协会肿瘤微环境专业委员会委员 中国临床肿瘤学会（CSCO）免疫治疗专业委员会委员 中国医药教育协会肺部肿瘤专业委员会委员 中国医疗保健国际交流促进会肿瘤免疫学分会委员 中国医疗保健国际交流促进会胸部肿瘤分会委员 DIA 临床科学专业委员会委员 CSCO 理事 CSCO 晚期 NSCLC 抗血管生成药物治疗中国专家共识 执笔人 Jacob Sands 教授 丹娜法伯癌症研究院Lowe胸部肿瘤中心副主任 哈佛医学院内科学助理教授 肿瘤内科医师，主攻胸部肿瘤与肺癌方向 临床及研究重点为小细胞肺癌，涵盖新型诊断技术与治疗策略 积极开展小细胞肺癌及非小细胞肺癌临床试验研究 研究方向包括肺癌筛查及肺癌筛查项目体系建设 丹娜法伯多项临床试验首席研究员，包含小细胞肺癌辅助治疗与新兴疗法相关研究 参考文献 [1]PAZ-ARES L, DVORKIN M, CHEN Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial[J]. Lancet, 2019, 394: 1929-1939. [2]AHN M J, CHO B C, FELIP E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer[J]. N Engl J Med, 2023, 389(22): 2063-2075. [3]PÉROL M, YOSHIDA T, AHN M-J, et al. Tarlatamab–Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer[J]. N Engl J Med, 2026. DOI: 10.1056/NEJMoa2609482. [4]SANDS J, YOSHIDA T, AHN M-J, et al. Tarlatamab plus durvalumab vs durvalumab as first-line maintenance therapy following first-line durvalumab, platinum, and etoposide in ES-SCLC: primary analysis of the phase 3 DeLLphi-305 trial[J]. Ann Oncol, 2026, ESMO Congress 2026 (Madrid), LBA3. [5]PAULSON K G, LAU S C M, AHN M-J, et al. Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy in patients with extensive-stage small-cell lung cancer (DeLLphi-303): a multicentre, non-randomised, phase 1b study[J]. Lancet Oncol, 2025, 26: 1300-1311. [6]WERMKE M, et al. Updated results of tarlatamab with first-line therapy for ES-SCLC: DeLLphi-303[J]. Ann Oncol, 2026, ESMO Congress 2026 (Madrid), 3821P. 撰写：Cynthia 审校：Cynthia 排版：Atai 执行：Atai 本平台旨在为医疗卫生专业人士传递更多医学信息。本平台发布的内容，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。如该等信息被用于了解医学信息以外的目的，本平台不承担相关责任。本平台对发布的内容，并不代表同意其描述和观点。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。