Durvalumab

说明：欢迎约稿、业务洽谈、媒体合作及行业交流。如需加入行业交流群，或发现内容涉及侵权需修改，请联系小助手微信：Taaslabs18 君实终于公布了备受各界关注的数据，近段时间以来，君实生物股价大幅上扬，推动其上涨的主要因素，大多是对AACR相关进展，以及PD-1×VEGF双抗、EGFR×HER3 ADC的商务拓展（BD）预期。如今数据已出，我们可以详细对比分析一番了。 先给出结论，情况有喜有忧。喜的是，双抗JS207在结直肠癌和肝癌治疗领域的数据表现相当出色，具备开展商务拓展（BD）的充分可能性；忧的是，双抗ADC与同靶点的EGFR×HER3 ADC对照时，数据表现稍显逊色，这有可能是随访时间过短所造成的。 我们先来聚焦JS207，目前它在一线肝细胞癌（HCC）和一线转移性结直肠癌（mCRC）这两个适应症上同步开展研究。外界所看到的，是两张数据表格，其中最引人注目的，当属HCC的71.4%客观缓解率（ORR）和mCRC的67.7%客观缓解率（ORR）。这些数据十分亮眼，但也正因为如此亮眼，容易引发两种截然相反的误读：要么是过度亢奋，要么直接以“样本量太小”将其一笔带过。 这篇文章要做的，便是在这两种极端认知之间探寻出第三种解读方式——JS207真正的差异化优势究竟体现在何处，以及它到底需要达成怎样的证明，才能最大程度地实现出海目标。 这是关于肝癌一线治疗的数据表格，当下最为主流的治疗方案，便是O药联合BMS的CTLA - 4单抗。 观察JS207的数据时，人们最容易犯的错误，就是直接将它与已获批的注册级III期数据进行对比。看到71.4%与36%的对比，便得出“JS207碾压O药＋Y药”的结论。这一结论不仅不够严谨，在现实情况中更是根本站不住脚。 这里有两件事必须阐述清楚：样本量以及研究设计。 就HCC（肝细胞癌）方面而言，71.4%这个客观缓解率（ORR）源自NCT06954467试验的剂量探索期高剂量组，样本数n = 7。其置信区间大约在28%至96%之间——这意味着，这个数据的真实值有可能低至28%，也有可能高至96%，跨度接近70个百分点。倘若在7个人当中，有1个人从有效变为无效，ORR就会从71.4%下降到57.1%；要是再多1个人出现这种情况，ORR就降至42.9%。而且，该研究没有独立影像核查（BICR），也未设置随机化对照，所有评估均依靠研究者自行评判。与之形成鲜明对比的是，CheckMate 9DW是样本数n = 335的随机对照III期试验，IMbrave150是样本数n = 336的III期试验，其评估标准采用的是独立影像委员会（BICR/IRF）。君实的数据尽管十分出色、令人惊艳，但无奈样本量实在太小，我们可以说它存在很大的机会，但仍需继续等待后续结果。 在mCRC（转移性结直肠癌）领域，情况虽稍有改善，但本质并无二致。JS207联合XELOX方案取得的67.7%客观缓解率（ORR），是基于31名可评估患者得出的数据，且中位随访时间仅仅为4.19个月。将其与AK112联合FOLFOXIRI方案（n = 22）取得的81.8% ORR，以及SSGJ - 707联合XELOX/FOLFOX方案（n = 68）取得的58.8%至62.5% ORR进行对比时，除了要考虑化疗方案骨架强度存在系统性差异这一因素外，样本量和随访时间的差异，实际上也并不足以支持直接进行数字层面的比对。 我们不妨在这里深入阐释一下，康方生物的数据为何如此亮眼：关键在于其联用的化疗药物存在差异。康方生物采用的是三药联合化疗方案，其中伊立替康（作为第三种药物）的加入，从根源上改变了肿瘤所处的微环境，进而放大了PD - 1×VEGF双抗的协同作用效果。 但三药方案并非没有代价——从历史数据来看，FOLFOXIRI方案的3/4级不良事件（AE）发生率约为55 - 70%，明显高于XELOX方案的约30 - 35%。所以，AK112能取得高客观缓解率（ORR），是以承受更高毒性为代价换来的，并非源于分子层面的优势。JS207和SSGJ - 707选择两药方案，是出于主动降低风险、扩大适用患者群体的策略考量，并非无奈之下的次优选择。 那么对于JS212而言，最值得关注的差异点究竟是什么呢？笔者认为，关键还在于肝癌领域。一线肝细胞癌（HCC）治疗市场，如今已近乎被瓜分完毕。阿特珠单抗+贝伐珠单抗（atezo + bev，2020年获FDA批准）、度伐利尤单抗+曲美木单抗（durvalumab + tremelimumab，2022年获批）、纳武利尤单抗+伊匹木单抗（nivo + ipi，预计2025年4月，基于CheckMate 9DW研究，中位总生存期mOS为23.7个月，客观缓解率ORR为36%）。这三种治疗方案，涵盖了PD - 1/PD - L1、VEGF抗体和CTLA - 4，从治疗理念上几乎将免疫治疗与抗血管生成治疗的两两组合都覆盖到了。 JS207联合JS007若想在一线肝细胞癌（HCC）治疗领域站稳脚跟，其倚仗的并非又一套免疫与抗血管生成的两两组合方案，而是一种在HCC领域迄今尚未有人尝试过的三重免疫阻断设计：PD - 1/VEGF双特异性抗体（JS207）搭配独立的CTLA - 4抑制剂（JS007）。 从机制层面剖析，其内在逻辑并不复杂：HCC的免疫微环境呈现出以调节性T细胞（Treg）浸润以及血管内皮生长因子（VEGF）介导的血管异常为主要特征的抑制性状态。CTLA - 4在T细胞活化过程中处于上游环节——它能够扩增效应T细胞的数量，同时清除Treg细胞；而JS207所具备的PD - 1/VEGF双抗功能则可同时发挥两方面作用：PD - 1阻断能够解除对效应T细胞的抑制，VEGF阻断则可促使血管正常化，改善T细胞向肿瘤部位的归巢。这三个关键节点，理论上全面覆盖了免疫抑制的上游（CTLA - 4）、末端效应（PD - 1）以及物理屏障（VEGF）。 然而，理论逻辑清晰是一码事，实际数据表现又是另一码事。在一线HCC治疗领域，近期可作为竞品参照的是COMPASSION - 08研究（卡度尼利单抗+仑伐替尼），其B队列（15mg/kg，每3周一次，n = 28）的客观缓解率（ORR）为35.7%（95%置信区间：18.6 - 55.9%），中位无进展生存期（mPFS）为9.8个月，中位总生存期（mOS）尚未达到（随访时长27.4个月），中位缓解持续时间（mDoR）为13.67个月。这已然是目前在该设计空间内数据最为成熟的参照点——但即便样本量n = 28，置信区间的宽度仍达37个百分点，这充分表明HCC这一适应症对于小样本数据的考验极为严苛。 JS207的样本量n = 7，其置信区间宽得离谱；Cado联合Len方案所产生的毒性，主要源自仑伐替尼；而且这三组试验在设计以及入组人群方面，均不具有可比性。 COMPASSION - 08研究存在一个常被低估的复杂情况：仑伐替尼单独使用时，就能带来约18%至20%的客观缓解率（ORR）。所以，很难从35.7%这一合并数据中，单独分辨出卡度尼利单抗（cadonilimab）所做出的独立贡献。这意味着，COMPASSION - 08研究所证明的是“卡度尼利单抗+仑伐替尼”这一整体方案的有效性，而非卡度尼利单抗对一线肝细胞癌（HCC）免疫微环境的改变作用。 这正是JS207+JS007研究设计中最具价值的核心所在：其随机扩展期预先设定了1:1的对照模式——即JS207+JS007联合用药组与JS207单药组进行对比。只要双抗与CTLA - 4联用的机制逻辑能自洽——联合用药组的客观缓解率（ORR）显著高于单药组（预计差距达到或超过15至20个百分点），便能为“三重免疫封锁策略在肝细胞癌（HCC）治疗中具有增量价值”提供首个基于随机对照试验的证据。在一线HCC的免疫联合治疗方案研究领域，这无疑是独一无二的设计。一旦机制逻辑得到验证，君实生物极有可能重新定义肝癌一线治疗的新范式。 然而，在安全性方面有一个关键信号需要持续密切关注：治疗相关不良事件（TRAE）中，丙氨酸氨基转移酶（ALT）升高和天门冬氨酸氨基转移酶（AST）升高的比例各占50%。对于HCC患者群体而言，这一比例所带来的风险远高于其他实体瘤患者——由于HCC患者的基础肝功能储备相对有限，即便Child - Pugh分级为A级的患者亦是如此。倘若高剂量JS007所引发的CTLA - 4相关效应与免疫性肝炎叠加，很可能在扩展期成为阻碍研究推进的实际瓶颈。这是目前最需要警惕的信号，其重要性远超过单纯的数字表现。 基于上述考量，我们预测HCC相关产品的销售峰值将达到30亿元。 在结直肠癌（CRC）领域其实没什么太多可赘述的。我们都清楚，微卫星稳定型（MSS）CRC堪称一片亟待开发的蓝海市场，就目前而言，完全有足够的空间容纳三款双特异性抗体药物展开竞争。不过，当下最关键的问题在于，JS207的疗效能否保持稳定，其客观缓解率（ORR）能否持续稳定在60%以上。倘若JS207真能达到这一疗效标准，那么我们完全有理由为JS207在一线CRC治疗市场的销售峰值设定得更高一些，达到30亿。 也就是说，这两款药品的销售峰值已然攀升至60亿元。鉴于当下PD - 1×VEGF赛道竞争极为激烈、内卷严重的状况，即便采用两倍的市销率（PS）进行估值，且暂不将肺癌适应症纳入考量，这条产品管线目前的估值也已高达120亿元！ 这无疑是值得欣喜的一面，然而，接下来也有令人忧虑的情况。JS212在针对奥希替尼耐药患者的治疗中，疗效未能达到预期。我们仅聚焦于1.8mg/kg及以上剂量组，其客观缓解率（ORR）仅有30%。 这一疗效数据与BL - B01D1相比，差距十分显著；和SKB264相比，也远远不及；甚至与dato - dxd相比，也处于劣势，要知道dato - dxd单药治疗的ORR就达到了42.7%（95%置信区间：33.6% - 52.2%），其中奥希替尼经治亚组的ORR更是高达44.8%（95%置信区间：34.6% - 55.3%）。 当然，我们尚可抱有一丝期待，毕竟当前随访时长过短，仅有三个月。或许随着随访时间的延长、数据的进一步积累，会有更多原本处于疾病稳定（SD）状态的患者转化为部分缓解（PR）状态。 不过，在其他癌种的治疗中，这两者的表现倒是较为接近，食管鳞癌（ESCC）和乳腺癌的相关数据如下图所示。 当下最为关键、重中之重的问题，便是后续JS207与JS212联合用于二期临床试验的数据揭晓情况，这一结果预计在今年年内就会公布。我多次提及过这个关键叙事，它堪称当下中国创新药领域最重要的叙事线索之一。尽管JS212目前的表现稍显逊色，但我们仍应给予它更多的随访时间，让它有机会证明自身的价值。 综合各方面因素考量，可从以下三个维度进行分析： HCC领域：采用三重免疫阻断策略，内部设置随机对照环节，聚焦于一个此前医药界尚未有人解答的难题。这个答案预计会在2026至2027年随机扩展期的中期数据中得以揭晓。 mCRC领域：以两药XELOX方案作为基础框架，主动舍弃三药方案所带来的短期数据上的优势，转而追求毒性的可控性以及更广泛的适用患者群体。只有当HARMONi - GI6在相同的化疗强度基准下公布相关数据时，JS207才真正进入差异化验证的关键阶段。 还有第三个维度，也是当下最需要着重强调的：JS207与JS212的联合用药临床试验正在推进当中，这是整个君实生物产品管线叙事中最具灵活性和潜力的部分。一旦试验结果超出预期，君实生物就不只是在单纯售卖两个独立的药品资产，而是在讲述一个“双平台协同增效”的精彩故事——对于商务拓展（BD）合作方而言，这意味着谈判的筹码从单一产品管线升级到了联合开发（co - co）层面。 特瑞普利单抗演绎的是先发制人的故事，其核心竞争力在于抢占先机的速度优势。而JS207所讲述的则是平台化发展的故事，它的立足点在于产品管线的宽度以及不同产品间的协同效应。JS212的加入，让原本单一层次的平台叙事，成功升级为更具深度和广度的双层架构。 此次数据公布，说实话，对君实生物的市值必然会产生较大幅度的波动，商务拓展（BD）方面的合作预期也可以持续释放。接下来，就让我们共同期待君实生物双抗与双抗ADC联用方案后续的精彩表现。 ►►► CGT创新合作交流群 CGT Asia 亚洲细胞与基因治疗创新峰会旨在搭建高效合作平台， 促进研究人员、临床医生、企业家与投资人之间的深度对话与实质性合作，深入探讨技术创新与临床转化，破解研发、工艺、产业化难题，汇聚各方力量，加速颠覆性疗法上市，使更多疾病得以治愈与改善。 即刻扫码加入 “CGT创新合作交流群” 免责声明： 本文内容来源于官方网站，旨在为大家提供知识共享，不构成任何专业建议。本资料中含少量AI生成内容，同时所涉及的图片、及文字仅供参考，目的是为了将好的内容分享给更多人，版权依旧归原作者所有，若侵犯肖像权或者著作者权等知识产权，请联系我方删除。 信息来源：公众号潮药Bar END 近期峰会活动 谈思特别推荐 *谈思生物特色社群* 谈思生物聚焦国内外生物医药产业最新动态，专注为细胞治疗、基因治疗、类器官、核酸、疫苗、医美、神经系统、核药、医药制造等细分领域提供线上线下交流分享的专业平台，赋能中国生物医药产业发展，助力打造全球生物医药产业高地。每年谈思生物举办数十场线上线下品牌活动，拥有数十个生物医药行业精品社群，覆盖Novaris、赛诺菲、复宏汉霖、齐鲁制药、药明康德、辉瑞、阿斯利康、百济神州、赛默飞世尔等百家国内外领先的药企、CRO/CDMO等，已经服务上万名生物医药行业上下游从业者。 专属社群：细胞治疗、基因治疗、医美、类器官、核酸药物、生物医药、RNA疫苗、工艺技术、中枢神经系统、核药、医药制造等，现专题社群仍然开放，入满即止。  演讲/赞助/参展/进群/媒体/直播 133 4168 3667 sara.an@taaslabs.com

Encouraging early results catalyze continued investigation in the MATISSE Phase 2 study evaluating IPH5201, a first-in-class anti-CD39 monoclonal antibody, in combination with durvalumab and chemotherapy in resectable NSCLC; these results will be presented at the Clinical Trials Plenary Session at the AACR Annual Meeting 2026, on April 21 MARSEILLE, France--(BUSINESS WIRE)-- #immunotherapy --Regulatory News: Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“ Innate ” or the “ Company ”), today announced that interim results from the MATISSE Phase 2 study evaluating IPH5201 in combination with durvalumab and platinum-based chemotherapy in resectable non-small cell lung cancer (NSCLC) will be presented in one of the Clinical Trials Plenary Sessions at the American Association for Cancer Research (AACR) Annual Meeting 2026, taking place April 17–22, 2026 in San Diego, California. The MATISSE study ( NCT05742607 ) is a single arm Phase 2 clinical trial evaluating perioperative IPH5201, an anti-CD39 blocking antibody, in combination with perioperative durvalumab (anti-PD-L1) in addition to neoadjuvant platinum-based chemotherapy in previously untreated patients with resectable NSCLC. The trial is designed to assess whether dual inhibition of the CD39 and PD-L1 pathways, together with chemotherapy, can enhance anti-tumor immune responses and improve clinical outcomes in early-stage lung cancer. These results follow a pre-planned interim analysis on 40 patients. The combination of IPH5201 with durvalumab and chemotherapy demonstrated higher pathological complete response (pCR) rates compared with the benchmark set by durvalumab plus chemotherapy alone. Notably, pCR was 35.7% and 50% in patients with tumors expressing PD-L1 ≥1% and PD-L1 ≥50%, respectively. Based on these results, the study continues to recruit patients with tumors expressing PD-L1≥1%. “ Patients with resectable NSCLC remain at significant risk of recurrence, underscoring the need for novel perioperative treatment strategies. Disrupting the adenosine pathway through CD39 inhibition with IPH5201, in combination with PD-1 blockade and chemotherapy, could enhance anti-tumor immune responses—particularly in patients with PD-L1 positive tumors, where we observed up to 50% pCR rate in the MATISSE trial. This signal will be further investigated as we complete enrollment of the study in the PD-L1-positive population ,” commented Dr. Sonia Quaratino, Chief Medical Officer of Innate Pharma . The presentation will be available in the publication section of Innate Pharma’s website . Abstract details Dual CD39 and PD-L1 inhibition: Interim results from the Phase 2 MATISSE trial of IPH5201 plus durvalumab and platinum-based chemotherapy in patients with resectable NSCLC Abstract Code: CT231 Session: CTPL04 – Advances in Immunotherapy Session Date/Time: Tuesday, April 21, 2026, 10:45 – 11:00 AM PDT Presenter: Pr. Fabrice Barlesi, CEO of Institut Gustave Roussy About IPH5201 IPH5201 is a first-in-class monoclonal antibody targeting CD39, a key immunosuppressive enzyme in the adenosine pathway. CD39 is expressed on tumor-infiltrating immune and stromal cells and contributes to immunosuppression by degrading extracellular adenosine triphosphate (ATP) into adenosine monophosphate (AMP), which is then further degraded into adenosine by CD73. By blocking CD39, IPH5201 promotes the accumulation of immunostimulatory ATP and reduces the production of immunosuppressive adenosine, thereby enhancing anti-tumor immune responses. IPH5201 is being co-developed in collaboration with AstraZeneca and is currently being evaluated in the Phase 2 MATISSE trial (NCT05742607), a multicenter study investigating perioperative treatment with IPH5201 in combination with durvalumab (anti-PD-L1) and platinum-based chemotherapy in patients with resectable non-small cell lung cancer (NSCLC). The MATISSE trial is designed to assess anti-tumor activity, including pathological complete response, and safety, with the goal of determining whether dual inhibition of the CD39 and PD-L1 pathways, in combination with chemotherapy, can enhance anti-tumor immunity and improve clinical outcomes in early-stage NSCLC. About Innate Pharma Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Leveraging its expertise on antibody-engineering and innovative target identification, Innate Pharma is developing innovative and differentiated next-generation antibody therapeutics. Innate Pharma is advancing a portfolio of differentiated potential first- and/or best-in-class assets, focused on areas of high unmet medical need, including IPH4502, a differentiated Nectin-4 ADC developed in solid tumors, lacutamab, an anti-KIR3DL2 antibody developed in cutaneous T cell lymphomas and peripheral T cell lymphomas, and monalizumab, an anti-NKG2A antibody developed in collaboration with AstraZeneca in non-small cell lung cancer. Innate Pharma has established collaborations with leading biopharmaceutical companies, including Sanofi and AstraZeneca, as well as renowned academic and research institutions, to advance innovation in immuno-oncology. Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US. Learn more about Innate Pharma at and follow us on LinkedIn and X. Information about Innate Pharma shares ISIN code Ticker code LEI FR0010331421 Euronext: IPH Nasdaq: IPHA 9695002Y8420ZB8HJE29 Disclaimer on forward-looking information and risk factors This press release contains certain forward-looking statements, including those within the meaning of applicable securities laws, including Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These are based on the management’s current beliefs, expectations and assumptions about future events, conditions and results and on information currently available to the management. When used in this press release, certain words, including “anticipate,” “plan,” “believe,” “can,” “could,” “estimate,” “project,” “expect,” “may,” “might,” “potential,” “expect” “should,” “will,” or the negative of these and similar expressions, identify forward-looking statements. Although the Company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, enrolment, results and other milestones of its preclinical trials, the Company’s reliance on third parties to manufacture its product candidates, the Company’s commercialization efforts and the Company’s continued ability to raise capital to fund its development and product trials given its current cash position and the impact an inability to raise further financing would have on the Company’s ability to meet its financial or business objectives. For an additional discussion of risks and uncertainties, which could cause the Company's actual results, financial condition, performance or achievements to differ materially from those contained in the forward-looking statements, please refer to the Risk Factors (“Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (“AMF”), which is available on the AMF website or on Innate Pharma’s website, and public filings and reports filed with the U.S. Securities and Exchange Commission (“SEC”), including the Company’s Annual Report on Form 20-F for the year ended December 31, 2025, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public by the Company. References to the Company’s website and the AMF website are included for information only and the content contained therein, or that can be accessed through them, are not incorporated by reference into, and do not constitute a part of, this press release. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by the Company or any other person that the Company will achieve its objectives and plans in any specified time frame or at all. The Company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country. Contacts For more information Investors & Media Relations Innate Pharma Stéphanie Cornen stephanie.cornen@innate-pharma.fr Investor Relations investors@innate-pharma.fr Media communication@innate-pharma.fr