3821P
Sustained survival with extended follow-up of tarlatamab plus anti-PD-L1 as first-line maintenance (1LM) after chemoimmunotherapy for extensive-stage small cell lung cancer (ES-SCLC): DeLLphi-303 phase 1b study
https://esmocongress.esmo.org
ESMO 2026
2026 年 10 月 23–27 日 · Madrid · 共 3194 条
tarlatamab
晚破23 人 · 28 条 · 3 篇摘要
本事件热度走势
当前热度 15·可比范围峰值 15（10月25日 02:00）·近 24 小时可比范围变化 –·当前参与者 18
参与者计数18
热度走势
深度解读
Tarlatamab（AMG 757）是靶向DLL3×CD3的双特异性T细胞衔接器，DLL3在大多数SCLC细胞表面高表达而在正常组织表达极低，使其成为有吸引力的治疗靶点[4]。这一资产的临床证据链已相当完整：I期研究纳入107例复发/难治SCLC患者，细胞因子释放综合征为最常见治疗相关不良事件（52%，3级仅1例），并报告1例5级肺炎[2]；II期研究中220例既往治疗患者接受每两周静脉给药，10 mg组客观缓解率40%（97.5% CI 29-52）、100 mg组32%，缓解者中59%（40/68）缓解持续时间至少6个月[1]；2025年发表的三期研究将509例铂类化疗后进展的患者随机分至tarlatamab（254例）或化疗（255例，托泊替康/卢比替康/氨柔比星），主要终点总生存期显著获益[3]。该药已于2024年以IMDELLTRA®之名获批上市[5]。
本次会议上传出的信息包含两条线索。主线是现场帖对安进与阿斯利康数据的解读：tarlatamab与durvalumab的联合被确立为广泛期SCLC一线维持治疗的新标准，帖中同时点名卢比替康（pharmamar）作为利益相关方；但帖子未给出任何缓解率或生存期数字。另一条是同期Cancer Cell论文的摘要：tarlatamab对SCLC有临床疗效但疗效仍有限，研究者显示5-羟色胺（5-HT）可诱导免疫抑制性肿瘤相关巨噬细胞（TAM），肿瘤由此对tarlatamab产生耐药。
相对已有认识，这两条信息各推进了一步。其一，tarlatamab此前的证据全部建立在经治人群的单药治疗上[1][2]，其加速批准也是针对既往治疗后的患者[3]，若联合durvalumab真进入一线维持，意味着用药线数显著前移——而一线化疗-免疫治疗后多数患者快速复发[4]、约70%的SCLC诊断时即为广泛期[6]，维持治疗正是关键战场。其二，5-HT-TAM轴为「疗效有限」提供了机制解释，提示耐药并非单纯的靶点表达或T细胞衔接问题。
需要强调的是，现场帖只给出定性结论，联合方案的有效率、生存数据、剂量与安全性均未披露，「新标准」的说法有待正式数据确认；机制研究本身也承认tarlatamab疗效有限，联合策略能否绕开5-HT驱动的免疫抑制、CRS等已知安全性问题[2]在联合背景下如何演变，均属待确认事项。
参考来源
- 1.Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer · N Engl J Med 2023
- 2.Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study · J Clin Oncol 2023
- 3.Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy · N Engl J Med 2025
- 4.Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer · J Hematol Oncol 2023
- 5.Antibodies to watch in 2025 · MAbs 2025
- 6.Small Cell Lung Cancer: A Review · JAMA 2025
证据
3848P
Cytokine release syndrome in patients receiving tarlatamab for extensive-stage small cell lung cancer: A real-world analysis
https://esmocongress.esmo.orgLBA3
Tarlatamab plus durvalumab (durva) vs durva as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): Primary analysis of the phase 3 DeLLphi-305 trial
https://esmocongress.esmo.org现场
Christine Lovly, MD, PhD, FASCO@christine_lovly 引用@Presented at #ESMO26: In a prespecified interim analysis of a phase 3 trial involving patients with extensive-stage SCLC, the median overall survival was 21.1 months with tarlatamab–durvalumab maintenance therapy and 12.7 months with durvalumab alone. Full DeLLphi-305 trial results: https://nej.md/4iveIgW @myESMO
Julien Mazieres@JulienMazieres Rami Manochakian MD, FASCO@RManochakian 引用@🚨🔥@OncoAlert Hot off the press. Just published @NEJM in conjunction with presentation @myESMO #ESMO26 the long-awaited #PracticeChanging results of: ⭐️#DeLLphi305 phase 3 trial of: ❇️1st line maintenance #Tarlatamab + #Durvalumab) vs #Durvalumab alone in patients with #ExtensiveStage #SmallCell #LungCancer after initial induction Tx with #Chemo + Durvalumab. Study showed: ‼️#Impressive statistically significant & clinically meaningful ⬆️#OverallSurvival Benefit. ✅#mOS: 21.1 vs 12.7 months (HR 0.42) ✅12-month OS: 79.4% vs 53.3% ✅#mPFS: 7.4 vs 1.9 months (HR 0.34) ⚠️ Grade ≥3 #AEs: 46.8% vs 40.6% * In Tarlatamab arm: #CRS: 49.6% (Grade ≥3: 0.4%) #ICANS: 1.1% (Grade ≥3: 0%) 👇🏻 https://www.nejm.org/doi/full/10.1056/NEJMoa2609482?query=featured_home
Rami Manochakian MD, FASCO@RManochakian FJ ⭐️⭐️+⭐️@pistoto2017 Giannis Mountzios@g_mountzios Prof Tom John@TommyJohn00 C. Michael Gibson MD@CMichaelGibson Mustafa Özdoğan, MD@ozdogan_md 引用@Presented at #ESMO26: In a prespecified interim analysis of a phase 3 trial involving patients with extensive-stage SCLC, the median overall survival was 21.1 months with tarlatamab–durvalumab maintenance therapy and 12.7 months with durvalumab alone. Full DeLLphi-305 trial results: https://nej.md/4iveIgW @myESMO
Hidehito HORINOUCHI@HHorinouchi 引用@🆙#ESMO26 Presidential Symposium I: #LCSM 🔥DeLLphi-305: Tarlatamab Plus Durvalumab (Durva) vs Durva as 1L Maintenance (1LM) Therapy Following Durva, Platinum, and Etoposide in Extensive-Stage Small Cell Lung Cancer (ES-SCLC): Primary Analysis of the Phase 3 Trial 🎙️ @sands_jacob 🔢LBA3 🎯Met Primary Endpoint: Significantly Improved OS 🎯mOS 21.1 vs 12.7m, HR 0.42 🎯mPFS 7.4 vs 1.9m, HR 0.34 🎯ORR 26.4% vs 4.1% 🎯CRS 49.6% (Mostly Low Grade), No Fatal Events ☑️NCT06211036 🔗 https://cslide.ctimeetingtech.com/esmo2026/attendee/confcal/show/session/346 @OncoAlert @Larvol @myESMO @IASLC
Anirban Maitra@Aiims1742 Tian Zhang, MD, MHS, FASCO (@tiansterzhangmd.bsky)@TiansterZhang Jose Fernando Moura, PhD@FernandoOnco @myESMO #Tarlatamab #sclc #ESMO26 @StephenVLiu @BalazsHalmosMD @OncoAlert
暂无中文译文，显示英文原文。
FJ ⭐️⭐️+⭐️@pistoto2017 引用@Let’s take a look at #DeLLphi-305: the trial yields poor results in the "Americas," so you bring in a large number of Asian patients (±40%) #sclc #ESMO26 Opinions??? @StephenVLiu @drshieldsmd @Tony_Calles @LuisPaz_Ares @lungoncdoc @Annechiangmd @LealTiciana @latina @MartinReck2
暂无中文译文，显示英文原文。
VJ Oncology@VJOncology KOL Pulse AI@KolPulseAI Correo Farmacéutico@CFarmaceutico David Heredia.@HerediaOncologo Diario Médico@diariomedico Dr. Estela Rodriguez@Latinamd FJ ⭐️⭐️+⭐️@pistoto2017 引用@@pistoto2017 Very relevant question! Platinum rechallenge or lurbinectedin may be options. But optimal 2L sequencing after tarlatamab maintenance remains an important unanswered question!
暂无中文译文，显示英文原文。
Dana-Farber News@DanaFarberNews Pharma Jonpi . / 1.1 / .@pharma_jonpi Pharma Jonpi . / 1.1 / .@pharma_jonpi Pharma Jonpi . / 1.1 / .@pharma_jonpi 顶刊论文（社媒热度）精选 肺神经内分泌癌通过血清素诱导免疫抑制性巨噬细胞，驱动tarlatamab耐药
DLL3高表达的肺神经内分泌癌通过上调TPH1增加血清素（5-HT），诱导HTR7表达的免疫抑制性肿瘤相关巨噬细胞（TAM），削弱CD8+ T细胞功能并驱动tarlatamab耐药。
推荐理由：研究将NEC来源的5-HT-HTR7轴与TAM免疫抑制及tarlatamab耐药相连，敲除NEC中的TPH1或TAM中的HTR7可恢复CD8+ T细胞功能。
同题 tarlatamab · 23 人还没有互动Cancer Cell精选 肺神经内分泌癌通过血清素诱导免疫抑制性巨噬细胞，介导对T细胞engager tarlatamab的耐药
Nomura等发现肺神经内分泌癌通过肿瘤来源血清素经HTR7通路塑造免疫抑制性巨噬细胞，介导对tarlatamab与ICB的耐药。该神经免疫机制在SCLC与LCNEC中均成立，并指出HTR7是潜在的可成药治疗脆弱点。
推荐理由：解析肺神经内分泌癌中肿瘤来源血清素经HTR7塑造免疫抑制性巨噬细胞、削弱tarlatamab与ICB的T细胞应答机制，为此类耐药研究提供可迁移的线索。
同题 tarlatamab · 23 人还没有互动监管与产业动态 ESMO：勃林格殷格海姆展示晚期DLL3双抗挑战安进Imdelltra
FierceBiotech报道，在ESMO会议上，勃林格殷格海姆展示了针对DLL3的晚期临床管线数据，旨在挑战安进的Imdelltra（tarlatamab）在小细胞肺癌领域的地位。