Pembrolizumab

说个反直觉的事。 全球卖得最好的抗癌药，不是化疗，不是靶向药，是一类叫PD-1/PD-L1抑制剂的免疫药。 默沙东的K药，2025年全球卖了接近300亿美元，单品种销售额已经超过了全球所有化疗药的总和。 K药做了一件什么事？它不杀癌细胞。它只是把免疫系统被癌细胞踩住的刹车松开，让T细胞自己去杀。 这个逻辑太漂亮了。化疗和靶向药是外力介入，药在癌细胞死，药停癌细胞长。 免疫治疗是重启人体自身的抗癌能力，一旦起效，可能管好几年。部分晚期黑色素瘤患者用K药活了超过十年，这在化疗时代完全不可想象。 但PD-1不是免疫治疗的终点，它只是第一道门。门推开之后，整个免疫治疗赛道正在往三个方向裂变。每一个方向都可能是下一个千亿市场。 一 PD-1的问题是太粗糙了。 它的原理是松开T细胞的一个刹车。但T细胞杀癌细胞的过程极其精密，刹车不止一个。癌细胞也很聪明，PD-1这条路被堵上了，它会激活别的免疫逃逸通路。 这就导致一个结果：PD-1单药治疗有效率平均只有20%到30%。 肝癌、胃癌、胰腺癌这些“冷肿瘤”里效果更差，有效率不到15%。大部分患者对PD-1原发耐药，或者刚开始有效后来继发耐药。 怎么办？方向有两个。一个是把PD-1跟别的靶点联合用，同时松好几个刹车。另一个是让免疫细胞更精准地找到癌细胞，给它装个导航。 双抗就是这个逻辑的产物。 康方生物的卡度尼利单抗是全球第一个PD-1/CTLA-4双抗，2022年在中国获批治疗宫颈癌，2025年又批了胃癌适应症。 它的设计极其巧妙：一个抗体分子上同时带两个靶点，PD-1这边松开T细胞刹车，CTLA-4那边再松一个。 而且CTLA-4的结合被设计成在肿瘤微环境里才激活，不在全身乱开，副作用小得多。 临床数据很炸。在PD-1耐药的胃癌患者里，卡度尼利单抗把有效率重新拉回到接近一线水平。 这个意义怎么强调都不过分，它等于是在PD-1无效的人群里重新激活了免疫治疗。 2025年卡度尼利单抗卖了接近60亿，而且还在高速增长。康方生物靠这一个品种市值从几十亿涨到接近千亿，是国内创新药企里最猛的黑马。 但卡度尼利单抗的成功还有一个更深远的影响，它证明了双抗这个技术路线在肿瘤免疫上是成立的。 现在全球有超过100个双抗在临床阶段，阿斯利康、罗氏、默沙东都在追。 国内除了康方，信达、恒瑞、石药也在推自己的双抗管线。未来三到五年，双抗会从康方一家独大变成多强争霸。 这个竞争烈度会拉高所有双抗企业的研发成本和销售费用，但也会加速双抗在更多适应症上的渗透，整个盘子会快速做大。 二 如果说PD-1是松开刹车，那双抗就是同时松好几个刹车。刹车全松了，T细胞活性拉满，但对某些“冷肿瘤”还是不够。 这些肿瘤把自己伪装得跟正常组织一模一样，T细胞根本认不出来，刹车全松也没用。 这个时候需要另一条技术路线：给T细胞装导航。 CAR-T是最极致的版本。把患者自己的T细胞抽出来，在体外用基因工程装上一个人工受体，能精准识别癌细胞表面的特定靶点，再把T细胞输回去。 这个装了导航的T细胞一旦在体内找到癌细胞，激活效率是自然免疫反应的几千倍。 诺华的Kymriah和吉利德的Yescarta是最早获批的两个CAR-T。在急性淋巴细胞白血病和弥漫大B细胞淋巴瘤上，完全缓解率超过80%。 注意是完全缓解，不是部分缓解。肿瘤全部消失，影像学查不到。这个疗效在所有抗肿瘤治疗里都是天花板级别。 但CAR-T有两个致命局限。一个是实体瘤效果很差，在肺癌、肝癌、胃癌上尝试了很多年，效果都不理想。 实体瘤的肿瘤微环境太复杂，CAR-T进去了被各种机制压制住，根本展不开。 另一个是成本太高，一次治疗费用120万到200万人民币，而且全部自费，医保不报销。 目前CAR-T在国内的商业化只能覆盖极少数富裕的血液肿瘤患者，年销售额加起来不到十亿。如果实体瘤突破不了，CAR-T永远是一个小而美的技术，成不了大品种。 传奇生物的BCMA CAR-T西达基奥仑赛在多发性骨髓瘤上拿到了全球最好的数据，2025年在美国卖了接近20亿美元，是国内创新药出海最成功的案例。 但它也是血液肿瘤，实体瘤的突破还在等。 TCR-T和TIL是另外两个方向的细胞治疗。TCR-T能识别细胞内抗原，在滑膜肉瘤和宫颈癌上已经拿了突破性疗法认定。 TIL是直接把肿瘤组织里已经识别了癌细胞的那群T细胞拿出来扩增再输回去，在黑色素瘤和宫颈癌上早期数据很漂亮。 这两个方向如果能跑出阳性III期，实体瘤的细胞治疗就能撕开一个口子。 三 免疫治疗还有第三条路：肿瘤疫苗。 这个跟平时打的流感疫苗完全不是一回事。肿瘤疫苗不是用来预防癌症的，是治疗用的。 它的逻辑是把肿瘤细胞的突变蛋白做成疫苗打回体内，训练免疫系统专门去识别和攻击携带这些突变的癌细胞。 Moderna和默沙东联合开发的mRNA-4157，是一种个体化肿瘤疫苗。 每个患者做手术把肿瘤切下来，做全外显子测序，找到这个肿瘤特有的突变蛋白，然后针对这些突变定制一个mRNA疫苗。 打回体内之后，树突状细胞把这些突变信息呈递给T细胞，T细胞就学会了识别这个患者的特定癌细胞。 这个技术太新了，目前只在二期临床。但在高危黑色素瘤术后辅助治疗的数据极其惊人：跟K药单药比，疫苗加K药把复发风险再降了44%。 44%的风险下降是什么概念？如果一个高危黑色素瘤患者术后用K药辅助治疗，三年内有30%概率复发。 加上肿瘤疫苗，复发率降到17%。这是叠加在PD-1基础上的额外获益，增量价值非常清晰。 默沙东已经启动了黑色素瘤和非小细胞肺癌的III期临床。如果数据能复制二期，肿瘤疫苗将成为免疫治疗的第三波浪潮。 但个体化疫苗的商业化是个巨大的挑战。每个患者都要单独测序、单独合成mRNA、单独质检放行，生产周期好几周，成本极高。 Moderna目前的定价策略是一针十几万美元。医保能不能覆盖、大规模生产能不能降低成本，是这条路能不能走通的关键。 四 从投资角度，免疫治疗赛道的投资逻辑分成三个层级。 第一层是PD-1和PD-L1的存量市场。K药一年300亿美元，O药、T药、I药、国产的卡瑞利珠单抗、信迪利单抗都在几十亿到上百亿的级别。 这个市场已经在往平台期走，增速放缓，竞争加剧，毛利率被集采和医保谈判压缩。投资机会不在整个品类，在谁能把PD-1做得更好用、更安全、能跟更多药物联用。 第二层是双抗和下一代免疫检查点抑制剂。康方生物的卡度尼利单抗是这一层的标杆，后续还有TIGIT、LAG-3、TIM-3等新靶点双抗在临床推进。 这个层级的投资确定性低于PD-1但弹性更大，赌的是临床数据能不能跑出来。 第三层是细胞治疗和肿瘤疫苗。这是未来十年的方向，也是风险最大、弹性最大的层级。 目前只有传奇生物的西达基奥仑赛跑出了确定性，大部分管线还在早期临床。赌的是五年后谁能成为细胞治疗领域的下一个K药。 （风险提示：本文基于药品审批信息、上市公司财报及行业公开数据梳理，内容仅供参考，不构成任何投资建议。文中提及公司仅作行业分析案例，不作为个股推荐。新药研发存在失败风险，药品审批和商业化存在不确定性。股市有风险，投资须谨慎。）

Aug. 3, 2026 -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to olomorasib as a monotherapy for the treatment of adult patients with advanced pancreatic cancer who have received at least one prior systemic therapy and have a KRAS G12C mutation, as determined by an FDA-approved test. Olomorasib is an investigational, potent and highly selective next-generation inhibitor of KRAS G12C. Olomorasib was previously granted Breakthrough Therapy designation, in combination with anti-PD-1 therapy KEYTRUDA (pembrolizumab), for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation and PD-L1 expression ≥ 50%, as determined by FDA approved tests. Breakthrough Therapy designation aims to expedite the development and review of drugs that are intended to treat a serious condition when preliminary clinical evidence indicate that the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over already available therapies that have received full FDA approval. Pancreatic cancer is diagnosed in approximately 60,000 people in the United States each year, with an estimated 50,000 deaths projected annually.1 Outcomes for patients with metastatic pancreatic cancer are typically poor, with a five-year survival rate under 5%.2 Growing evidence suggests outcomes for patients with KRAS G12C-mutant pancreatic cancer are worse than those without the mutation, underscoring a persistent gap in treatment and an opportunity to address a significant unmet need.3 There currently are no approved therapies that specifically target KRAS G12C-mutant pancreatic cancer. "Pancreatic cancer has historically been one of the most difficult-to-treat cancers and people whose tumors harbor a KRAS G12C mutation face limited options once their disease progresses," said Jacob Van Naarden, executive vice president, and president of Lilly Oncology. "This Breakthrough Therapy designation reflects the early potential we're seeing with olomorasib in this setting and the critical need for new treatment options. With now two Breakthrough Therapy designations across pancreatic and lung cancers, olomorasib continues to demonstrate broad potential clinical evidence across KRAS G12C-driven tumors and reflects our commitment to bringing meaningful new treatment options to patients living with these cancers." The FDA Breakthrough Therapy designation is based on encouraging preliminary results from the open-label, multicenter, Phase 1/2 LOXO-RAS-20001 study (NCT04956640) of olomorasib in patients with KRAS G12C-mutant, advanced solid tumors, including those with advanced pancreatic cancer who have received at least one prior systemic therapy. Lilly is studying olomorasib in KRAS G12C-mutant cancers in multiple studies. Details on the trials can be found by visiting clinicaltrials.gov. LOXO-RAS-20001 is an open-label, multicenter, Phase 1/2 study evaluating the safety, tolerability and preliminary efficacy of olomorasib in patients with KRAS G12C-mutant advanced solid tumors (NCT04956640). The study includes a Phase 1a dose escalation phase of olomorasib monotherapy in KRAS G12C-mutant solid tumors and a Phase 1b dose expansion and optimization phase which are evaluating olomorasib as a monotherapy and in combination with other treatments. Olomorasib (LY3537982) is an investigational, oral, potent, and highly selective next-generation inhibitor of the KRAS G12C protein. KRAS mutations account for approximately 85% of RAS-associated cancers in humans, including about 90% of pancreatic cancers, and KRAS G12C mutations occur in approximately 1% to 2% of patients with pancreatic cancer.4,5 Olomorasib was specifically designed to target KRAS G12C and has pharmacokinetic properties which allow for high predicted target occupancy and high potency when used as monotherapy or in combination.6 Olomorasib is currently being studied in the LOXO-RAS-20001 Phase 1/2 trial (NCT04956640) in patients with KRAS G12C-mutant NSCLC and other advanced solid tumors and in the pivotal, registrational SUNRAY-01 global study (NCT06119581) investigating olomorasib in combination with pembrolizumab with or without chemotherapy for first-line treatment of KRAS G12C-mutant advanced NSCLC, and the SUNRAY-02 (NCT06890598) global study investigating olomorasib in combination with standard of care immunotherapy in patients with resected or unresectable KRAS G12C-mutant NSCLC. Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. Endnotes & References Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820 [SEER] Surveillance, Epidemiology, and End Results (SEER). Cancer stat facts: pancreatic cancer. Published 2025. Accessed May 29, 2026. https://seer.cancer.gov/statfacts/html/pancreas.html Norton C, Shaw MS, Rubnitz Z, et al. KRAS mutation status and treatment outcomes in patients with metastatic pancreatic adenocarcinoma. JAMA Netw Open. 2025;8(1):e2453588. https://doi.org/10.1001/jamanetworkopen.2024.53588 Canon J. et al. Nature 2019, 575, 217-223 Salem M. et al. Ann Oncol 2021, 32 (3 Suppl): S218 Peng S-B, Si C, Zhang Y, et al. Abstract 1259: Preclinical characterization of Ly3537982, a novel, highly selective and potent KRAS-G12C inhibitor. Cancer Research. 2021;81(13_Supplement):1259-1259. doi:10.1158/1538-7445.am2021-1259 Luo J. KRAS mutation in pancreatic cancer. Semin Oncol. 2021;48(1):10-18. doi:10.1053/j.seminoncol.2021.02.003 Zeitouni D, Pylayeva-Gupta Y, Der CJ, Bryant KL. KRAS Mutant Pancreatic Cancer: No Lone Path to an Effective Treatment. Cancers (Basel). 2016;8(4):45. Published 2016 Apr 18. doi:10.3390/cancers8040045 Muller M, Tougeron D. KRAS G12C inhibitors: also a new promising new targeted therapy in advanced pancreatic adenocarcinoma?. Transl Cancer Res. 2023;12(12):3227-3232. doi:10.21037/tcr-23-1629 Pancreatic Cancer Treatment (PDQ®)–Patient Version. National Cancer Institute. Updated July 8, 2026. Accessed July 19, 2026. https://www.cancer.gov/types/pancreatic/patient/pancreatic-treatment-pdq Søreide K, Ismail W, Roalsø M, Ghotbi J, Zaharia C. Early Diagnosis of Pancreatic Cancer: Clinical Premonitions, Timely Precursor Detection and Increased Curative-Intent Surgery. Cancer Control. 2023;30:10732748231154711. doi:10.1177/10732748231154711 The content above comes from the network. if any infringement, please contact us to modify.