2026年4月24日，上海——PG国际（2696.HK）颁发，公司自主研发的沉组抗EGFR单克隆抗体pimurutamab（HLX07） 结合抗PD-1单抗H药 汉斯状®（斯鲁利单抗）及化疗，用于一线医治晚期鳞状非幼细胞肺癌（sqNSCLC）患者的随机、双盲、多中心、平行对照的II/III期临床钻研已在澳大利亚实现临床试验登记（CTN），迈出肺鳞癌一线医治领域的创新医治索求关键一步。
肺鳞癌医治困境亟待突破，EGFR高表白蕴含临床新机
肺癌是全球癌症有关殒命的首要原因，其中非幼细胞肺癌（NSCLC）约占全数肺癌病例的85%，蕴含鳞癌和非鳞癌亚型1。sqNSCLC约占NSCLC的20%–30%，其临床获益较非鳞癌更差2。表皮成长因子受体（EGFR）在多种实体瘤中普遍高表白，蕴含非鳞状和鳞状非幼细胞肺癌，被以为是肿瘤产生、进展及耐药的沉要驱动成分3。在全球NSCLC患者中，EGFR高表白的比例约为40%–89%（取决于病理分型、种族等成分）4-6，而在sqNSCLC患者中这一比例靠近90%4-5；贓GFR在该人群中的宽泛表白特点，索求以EGFR通路为基础、面向肺鳞癌全人群的一线结合医治战术，拥有明确的生物学合理性和临床索求价值。
值妥贴心的是，EGFR高表白与EGFR敏感突变并不等同，二者之间的有关性较低7。尤其在sqNSCLC人群中，经典敏感性EGFR突调换为罕见8。这意味着，无数EGFR高表白的鳞癌患者并不携带敏感性EGFR突变，因而难以从EGFR-TKI类靶向药中获益8。只管近年来，抗EGFR单抗结合化疗在肺鳞癌等疾病的医治中展示出肯定的临床获益基础9-10，以PD-1/PD-L1抑造剂为基础的免疫结合化疗也显著改善了晚期肺鳞癌的一线医治终局，但整体疗效仍有提升空间，临床上仍亟需新的结合医治战术11-21。
靶向与免疫协同，pimurutamab结合医治战术展示潜力
Pimurutamab是PG国际自主研发的一款抗EGFR单克隆抗体，具备更低的免疫原性和更优的EGFR靶点亲和力。同时通过Fc端刷新，显著耽搁其半衰期，3周的给药频率使其更适合与肿瘤免疫产品的临床联用。临床前钻研批注，pimurutamab相较同类抗EGFR单抗拥有更杰出的生物活性，在分歧肿瘤模型中均能显著抑造肿瘤细胞的成长，并与H药显示出很强的协同作用22。两者联用，不仅阻断EGFR成长信号，更同步激活免疫应答，极具结合协同医治潜力。
此前，pimurutamab结合斯鲁利单抗及化疗用于一线医治EGFR高表白晚期或转移性sqNSCLC的II期剂量索求钻研（HLX07-sqNSCLC-201）已获得积极了局，中位随访18.6个月与23.5个月的具体数据已先后在2025年世界肺癌大会（WCLC）及2025年11月进行的国际肺癌前沿及创新论坛上颁布。凭据最新的中位随访23.5个月分析了局，该规划在两个剂量组均显示出不变且悠久的抗肿瘤活性：客观缓解率（ORR）约为70%，疾病节造率（DCR）超过90%；其中高剂量组的中位无进展生计期（mPFS）达到17.4个月，低剂量组的mPFS在随访时仍未达到；两组的中位总生计期（mOS）及持续缓解功夫（mDOR）亦尚未达到。整体安全性可控，未观察到新的安全性信号。
本次钻研（HLX07-sqNSCLC-301）是一项评估pimurutamab结合汉斯状®和化疗对比慰藉剂结合汉斯状®或帕博利珠单抗和化疗，作为一线医治晚期sqNSCLC患者的随机、双盲、多中心、平行对照的II/III期临床钻研。钻研蕴含两个阶段，第一阶段为II期钻研，受试者将按1:1:1的比例随机分配至三组之一：A组为pimurutamab 1000mg结合斯鲁利单抗和化疗；B组为pimurutamab 600mg结合斯鲁利单抗和化疗；C组为慰藉剂结合斯鲁利单抗和化疗。每三周一次（Q3W），共4个周期，随后别离进入相应剂量的pimurutamab或慰藉剂结合汉斯状®的维持医治阶段。第一阶段的重要终点为独立影像评估委员会（BICR）评估的无进展生计期（PFS）及客观缓解率（ORR）。第二阶段为III期钻研，pimurutamab的给药剂量将凭据第一阶段的钻研了局确定。合格受试者将按1:1的比例随机分配至两组之一。试验组为pimurutamab结合汉斯状®和化疗，每三周一次（Q3W），共4个周期；后续接受pimurutamab结合斯鲁利单抗维持医治。对照组为慰藉剂结合帕博利珠单抗和化疗，每三周一次（Q3W），共4个周期；后续接受慰藉剂结合帕博利珠单抗维持医治。第二阶段的重要终点为BICR评估的PFS和总生计期（OS）。本次钻研的重要主张是评估pimurutamab结合汉斯状®和化疗对比慰藉剂结合汉斯状®或帕博利珠单抗和化疗一线医治晚期sqNSCLC患者的疗效。次要主张蕴含评估pimurutamab结合汉斯状®和化疗的安全性、药代动力学特点及免疫原性，并评估肿瘤组织EGFR表白、PD-L1表白与疗效的关系。
PG国际深度布局肺癌医治领域，已形成覆盖多种组织学类型、多个医治阶段、兼具免疫、靶向、抗血管与抗体偶联药物（ADC）等多机造的综合产品矩阵。公司主题产品H药 汉斯状®作为全球首个获批用于幼细胞肺癌一线医治的抗PD-1单抗，已在全球40多个国度和地域获批上市，在肺癌领域全面覆盖宽泛期幼细胞肺癌（ES-SCLC）、鳞状非幼细胞肺癌（sqNSCLC）及非鳞状非幼细胞肺癌（nsqNSCLC）等关键适应症的一线尺度医治，其一线医治局期限幼细胞肺癌（LS-SCLC）的国际多中心III期临床钻研亦已完玉成球入组。与此同时，贝伐珠单抗汉贝泰®进一步美满公司在肺癌领域的抗血管靶向医治布局，为晚期、转移性或复发性NSCLC患者提供了更可职守的高质量医治选择。在创新研发方面，公司全面推动多元机造、差距化优势凸起的创新管线。具备广谱抗肿瘤潜力的PD-L1 ADC HLX43作为潜在同类最优药物，已在肺癌等多个瘤种中展示“高效、低毒”的显著医治优势，并在钟注美、日、澳等多国启动临床试验；抗EGFR单抗pimurutamab与H药的结合医治规划在EGFR高表白鳞状NSCLC人群中开释出拥有突破性的临床信号，推动精准医治不休向前发展。此表，公司早期研颁布局还蕴含拟用于幼细胞肺癌医治的DLL3 x DLL3 x CD3 x CD28四特异性T细胞衔接器HLX3901，以及拟用于NSCLC医治的cMET x EGFR双抗ADC HLX48等。
未来，PG国际将持续深入肺癌领域创新布局，通过多元化的产品组合和全球化的临床开发，为患者带来更多突破性医治规划，创造更大的临床价值和社会效益。
参考文件
1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74: 229–63.
2. Wang Y, Safi M, Hirsch FR, et al. Immunotherapy for advanced-stage squamous cell lung cancer: the state of the art and outstanding questions. Nat Rev Clin Oncol 2025; 22: 200–14.
3. Normanno N, De Luca A, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366(1):2–16. DOI: 10.1016/j.gene.2005.10.018. PMID: 16377102.
4. Prabhakar CN. Epidermal growth factor receptor in non-small cell lung cancer. Transl Lung Cancer Res. 2015;4(2):110-118. doi:10.3978/j.issn.2218-6751.2015.01.01
5. Karlsen E-A, Kahler S, Tefay J, Joseph SR, Simpson F. Epidermal Growth Factor Receptor Expression and Resistance Patterns to Targeted Therapy in Non-Small Cell Lung Cancer: A Review. Cells. 2021; 10(5):1206. https://doi.org/10.3390/cells10051206
6. The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 489, 519–525 (2012). https://doi.org/10.1038/nature11404
7. Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, Colasacco C, Dacic S, Hirsch FR, Kerr K, Kwiatkowski DJ, Ladanyi M, Nowak JA, Sholl L, Temple-Smolkin R, Solomon B, Souter LH, Thunnissen E, Tsao MS, Ventura CB, Wynes MW, Yatabe Y. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med. 2018 Mar;142(3):321-346. doi: 10.5858/arpa.2017-0388-CP. Epub 2018 Jan 22. PMID: 29355391.
8. The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 489, 519–525 (2012). https://doi.org/10.1038/nature11404
9. Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31.
10. Pirker R, Pereira JR, von Pawel J, et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 2012 Jan;13(1):33-42.
11. Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 2018; 379: 2040–51.
12. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med 2022; 28: 2374–80.
13. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol 2021; 22: 198–211.
14. Johnson ML, Cho BC, Luft A, et al, and the POSEIDON investigators. Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: the phase III POSEIDON study. J Clin Oncol 2023; 41: 1213–27.n
15. Wang J, Lu S, Yu X, et al. Tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: a phase 3 randomized clinical trial. JAMA Oncol 2021; 7: 709–17.
16. Ren S, Chen J, Xu X, et al, and the CameL-sq Study Group. Camrelizumab plus carboplatin and paclitaxel as first-line treatment for advanced squamous NSCLC (CameL-Sq): a phase 3 trial. J Thorac Oncol 2022; 17: 544–57.
17. Zhou C, Wang Z, Sun Y, et al. Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial. Lancet Oncol 2022; 23: 220–33.2
18. Zhong H, Sun S, Chen J, et al. First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial. Lancet Respir Med 2024; 12: 355–65.
19. Zhou C, Wu L, Fan Y, et al. Sintilimab plus platinum and gemcitabine as first-line treatment for advanced or metastatic squamous NSCLC: results from a randomized, double-blind, phase 3 trial (ORIENT-12). J Thorac Oncol 2021; 16: 1501–11.
20. Zhou C, Hu Y, Arkania E, et al, and the ASTRUM-004 Investigators. A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004). Cancer Cell 2024; 42: 198–208.e3.
21. Fortunato Ciardiello, Fred R. Hirsch, Robert Pirker, Enriqueta Felip, Christian Valencia, Egbert F. Smit,The role of anti-EGFR therapies in EGFR-TKI-resistant advanced non-small cell lung cancer, Cancer Treatment Reviews, Volume 122, 2024, 102664, ISSN 0305-7372, https://doi.org/10.1016/j.ctrv.2023.102664.
22. Tseng,Yun-Chih Cheng, Chieh-Hsin Ho, Shih Chieh Chen, Yanling Wang, Eugene Liu,Hassan Issafras & Weidong Jiang (2021) Distinguishing features of a novelhumanized anti-EGFR monoclonal antibody based on cetuximab with superiorantitumor efficacy, Expert Opinion on Biological Therapy, 21:11, 1491-1507.