2025年9月8日，复宏汉霖（2696.HK）宣布，公司自主研发的创新型抗PD-1单抗H药 汉斯状®（斯鲁利单抗，欧洲商品名：Hetronifly®）肺癌领域九项研究最新结果在2025年世界肺癌大会（World Conference on Lung Cancer, WCLC）上发布。本次大会上，H药 汉斯状®三项研究最新结果以口头报告的形式发布，其中，H药 汉斯状®一线治疗晚期非鳞状非小细胞肺癌III期临床研究（ASTRUM-002研究）结果在大会上以口头报告的形式首次发布。H药 汉斯状®是全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，已在中国、英国、德国、印度、印度尼西亚、新加坡等近40个国家和地区获批上市, 覆盖全球近半数人口。
复宏汉霖自主研发的创新型单抗H药 汉斯状®，目前已全面覆盖肺癌一线治疗，获批用于治疗鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）、非鳞状非小细胞肺癌（nsqNSCLC）三项肺癌适应症，同时正在全球范围内积极推动一项H药联合化疗同步放疗一线治疗局限期小细胞肺癌（LS-SCLC）的国际多中心III期临床试验。
相关研究显示，斯鲁利单抗具有更强的PD-1内吞作用，减少T细胞表面留存的PD-1受体数目[1]，带来更快、更强的免疫激活效应。此外，斯鲁利单抗能够减少PD-1对免疫共刺激分子CD28的募集，从而减少磷酸化酶SHP2对CD28的去磷酸化作用，更大程度保留CD28传递的信号[2-4]，因此，斯鲁利单抗进一步提高了信号通路下游AKT蛋白的活性[5]，促进T细胞的持续、稳健活化。
显著延长nsqNSCLC患者无进展生存期
脑转移获益明确
在本次大会上，由中国医学科学院肿瘤医院石远凯教授作为牵头主要研究者，首次以口头汇报形式公布了H药联合化疗一线治疗晚期nsqNSCLC的III期临床研究（ASTRUM-002研究）结果。研究数据显示，H药联合化疗组的中位无进展生存期（mPFS）达到11.0个月，较化疗组显著延长5.4个月，疾病进展风险降低45%。脑转移亚组分析显示，在化疗基础上增加斯鲁利单抗可显著改善mPFS（8.1m vs 4.1m），加入贝伐珠单抗的治疗组mPFS仍有获益趋势（9.7m vs 8.1m）。此外，一项斯鲁利单抗联合贝伐珠单抗和化疗治疗初治nsqNSCLC伴脑转移的II期IIT研究（SUPER BRAIN研究）结果也入选大会简短口头报告，四药联合治疗脑转移的数据进一步验证ASTRUM-002的斯鲁利单抗联合贝伐珠单抗和化疗在脑转移人群的疗效。
ASTRUM-002：斯鲁利单抗联合化疗（联合或不联合HLX04）用于晚期非鳞状非小细胞肺癌的一线治疗
研究设计：
这是一项三臂、随机、双盲、多中心3期研究。患有局部进展期或转移性非鳞状非小细胞肺癌、不携带EGFR致敏突变和ALK/ROS重排、且无系统性治疗史的患者，按1:1:1比例随机分配接受斯鲁利单抗+HLX04+化疗（A组）、斯鲁利单抗+化疗（B组）或化疗（C组）。斯鲁利单抗和HLX04每3周给药一次。主要终点是盲态独立中心评估委员会评估根据RECIST 1.1版评估的无进展生存期（PFS）。次要终点包括其他疗效终点和安全性。
结果：
从2019年11月25日至2023年6月15日（数据截止日期），636名患者被随机分配到A组（n=212）、B组（n=214）或C组（n=210）。 中位随访时间分别为23.4个月（95%置信区间，21.6-24.9）、23.1个月（95%置信区间，21.4-25.6）和23.0个月（95%置信区间，20.7-25.6）。B组中位PFS显著长于C组（11.0个月 vs. 5.6个月；分层HR=0.55，95%置信区间0.43-0.69，P < 0.0001），达到了研究方案中规定的优效标准。A组相比B组在PFS方面观察到数值上的改善（12.6个月 vs. 11.0个月，HR=0.86，95%置信区间0.67-1.11，P=0.2529）。总生存期尚未成熟。其他疗效结果见表1。导致死亡的治疗相关不良事件在三组中分别发生10例（4.7%）、5例（2.3%）和7例（3.3%）患者中。
结论：
相比化疗，斯鲁利单抗联合化疗显著延长了局部进展期或转移性非鳞状非小细胞肺癌患者的PFS。相比斯鲁利单抗联合化疗，斯鲁利单抗联合贝伐珠单抗和化疗展示了PFS数值上的改善。两种联合治疗方案均安全性可控。
斯鲁利单抗联合贝伐珠单抗和化疗治疗初治非鳞状非小细胞肺癌伴脑转移的II期研究
研究设计：
这项单臂、II期临床试验旨在评估斯鲁利单抗联合贝伐珠单抗、培美曲塞及卡铂在未经治疗的伴有颅内转移的晚期非鳞状非小细胞肺癌（NSCLC）患者中的疗效与安全性。入组患者需为无症状或经脱水治疗后症状已控制的颅内转移者。治疗方案包括4至6个周期的诱导治疗（斯鲁利单抗联合贝伐珠单抗、培美曲塞和卡铂），后续进入维持阶段，使用斯鲁利单抗联合贝伐珠单抗及培美曲塞，直至疾病进展、出现不可耐受的毒性事件、死亡或治疗满两年。本研究的主要终点为颅内无进展生存期（iPFS）。颅内疗效评估采用改良版实体瘤疗效评价标准（mRECIST 1.1）。
结果：
中位iPFS为13.1个月，6个月和12个月iPFS率分别为91.3%和67.1%。中位sPFS为13.3个月。12个月OS率为71.3%。颅内ORR为84.6%，颅外ORR为64.1%，显示出强大的抗肿瘤活性。最常见的≥3级TRAEs包括白细胞/中性粒细胞计数减少、血小板计数减少和肝功能检查异常。未报告治疗相关性死亡。
结论：
斯鲁利单抗联合贝伐珠单抗和化疗一线治疗伴有脑转移的非鳞状非小细胞肺癌患者表现出有前景的颅内抗肿瘤有效性和可控的安全性。
肺癌一线全覆盖，
探索更广泛人群治疗潜力
同时，多项H药免疫联合疗法的IIT研究结果也入选本次大会简短口头报告、壁报导览和壁报展示等环节，这些研究探索了免疫联合疗法在EGFR-TKI耐药、肺癌围术期NSCLC患者等广泛人群中的治疗潜力，以及印证了H药在ES-SCLC更多亚组人群中的疗效。
评价贝伐珠单抗联合斯鲁利单抗及化疗治疗EGFR-TKI耐药的非鳞状NSCLC患者II期研究
结果：
本研究为一项多中心、单臂II期试验，纳入46名年龄18-70岁、ECOG PS 0-1、EGFR-TKI治疗后进展且未经免疫化疗的EGFR突变非鳞状NSCLC患者。符合条件者接受4-6周期HLX04（7.5 mg/kg）联合HLX10（300 mg）及标准化疗，后续进入HLX04+HLX10+培美曲塞维持治疗，直至疾病进展、不可耐受毒性或治疗满2年。ORR为47.8%（95%CI：32.9-63.0%），达到了预设的终点45.0%。mPFS为7.7个月(95% CI: 7.0 - NR)，OS尚未成熟（3/46）。中位缓解时间（TTR）和缓解持续时间（DoR）分别为1.5个月（95%CI：1.4 - 2.8）和6.2个月（95%CI：5.3 - NR）。 无脑转移的患者更可能获得更好的疗效（ORR：52.4% vs. 44.0%；mPFS：9.5 m vs. 7.1m）。 任何级别不良事件的发病率为80.4%（37/46），17名患者（37.0%）出现了≥3级不良事件。
结论：
这些结果表明，斯鲁利单抗联合剂量减少的贝伐珠单抗和以铂类为基础的双药化疗方案对EGFR-TKI耐药的非鳞状非小细胞肺癌患者表现出良好的疗效和可控的安全性。
斯鲁利单抗新辅助治疗局晚期非小细胞肺癌的一项前瞻性单臂研究
结果：
这是一项前瞻性、单臂临床研究，55例II–IIIB期（T4N2）、经评估为可切除或潜在可切除的NSCLC患者接受3个周期的新辅助治疗，方案为斯鲁利单抗（300 mg）联合化疗。影像学评估显示2名患者完全缓解（CR），38 名（90.5%）部分缓解（PR），2 名（4.8%）病情稳定（SD）。ORR为 95.2%（40/42），87.5%（35/40）的患者接受了胸腔镜切除术，R0 切除率为 100%。主要病理缓解（MPR）率为 67.5%（27/40），病理完全缓解（PCR）率为 37.5%（15/40）。55 名患者中有 20 名（36.4%，20/55）出现不良事件，其中 5 名（9.1%，5/55）出现≥3 级不良事件，6名患者因不良事件停止治疗，但无手术因治疗相关毒性而延迟，1名患者出现严重围手术期并发症（支气管胸膜瘘），经支架置入和保守治疗后痊愈。
结论：
中期研究结果表明，斯鲁利单抗联合化疗在局部晚期非小细胞肺癌患者的术前新辅助治疗中显示出良好的疗效和可控的安全性。
一项II 期SPUR研究：多周期低剂量放射治疗重塑免疫化疗在广泛期小细胞肺癌中的应用
结果：
这是一项Ⅱ期、单臂、多中心研究，旨在评估在ES-SCLC且对其广泛期疾病未接受过化疗的受试者中，低剂量放射治疗（LDRT）同步顺铂/卡铂联合依托泊苷的化疗方案并联合斯鲁利单抗的安全性和疗效。截至2025年7月31日，中位随访时间为17.9个月。经确认的ORR为84.8%（50/59；95% CI：73.0-92.8），DCR为88.1%（50/59；95% CI：77.1-95.1）。中位DoR为7.07个月（95% CI：3.97-9.33）。中位PFS为7.3个月（95%CI：5.9-11.6），6个月和12个月PFS率分别是61.1%（95%CI：49.8-74.9%）和31.5%（95%CI：21.5-46.0%）。肝转移患者的中位PFS显著短于无肝转移者（4.4 vs 10.7个月；p=0.002）。中位OS尚未达到。
结论：
适应性多周期LDRT联合免疫化疗在初治ES-SCLC中具有良好抗肿瘤活性和生存获益，且安全性可控。12例患者仍在接受治疗，长期随访持续进行中。
PS评分≥2的广泛期小细胞肺癌患者的一线免疫联合化疗结果：来自ASTRUM-005R的真实世界证据
结果：
ASTRUM-005R是一项在中国开展的全国性真实世界观察研究。主要终点为总生存期（OS）、真实世界无进展生存期（rwPFS）和总体反应率（ORR）。本次亚组分析集中于ECOG PS ≥2的患者。在本次分析中，共纳入了75名ECOG PS ≥2的患者，占ASTRUM-005R总体队列的11.8%。其中，71名患者为PS 2，4名患者为PS 3。中位随访周期为16.37个月（1.90-23.60）。 与PS <2的患者相比，较差的体能状态对rwPFS无显著影响（HR = 1.15，P = 0.366）。 PS ≥2患者的中位rwPFS为6.97个月（95% CI, 6.23-10.43），1年rwPFS率为26.62%（95% CI, 17.22-41.14）。 与总体队列相似，基线脑转移对rwPFS无显著影响（HR = 0.98，P = 0.953）。然而，肝转移患者的rwPFS显著短于无肝转移患者（4.93 vs. 10.30个月；HR = 1.95，P = 0.018）。与PS <2的患者相比，PS ≥2患者的OS较差（HR = 1.89，P < 0.001），中位OS为12.33个月（95% CI, 10.43-15.57）。 同样，脑转移对OS无显著影响（HR = 0.86，P = 0.640），而肝转移与较差的OS相关（9.67 vs. 14.03个月；HR = 3.01，P = 0.001）。在74名具有可测量疾病且至少接受过一次治疗后影像学评估的患者中，ORR为66.22%（95% CI, 54.28-76.81）。 ECOG PS ≥2患者的安全性特征总体与总体人群观察到的一致。 20名患者（26.67%）报告了不良事件（AEs），15名患者经历了免疫相关不良事件（irAEs），其中5名患者报告了≥3级irAEs。
结论：
本次对ASTRUM-005R研究的亚组分析表明，以斯鲁利单抗为基础的一线免疫化疗在ECOG PS ≥2的广泛期小细胞肺癌患者中仍然具有临床疗效和可行性。 肝转移与较差的预后相关，但脑转移则没有。这些结果支持免疫化疗即使在传统上被排除在临床试验之外的患者中也可能具有益处，值得在前瞻性研究中进一步检查和验证。
一线免疫化疗在广泛期小细胞肺癌中的荟萃分析：ECOG 体能状态评分≥2 是否影响生存结局？
结果：
这项荟萃分析评估了ES-SCLC患者中，ECOG PS ≥2的患者接受一线免疫化疗的生存获益。汇总分析显示，在新诊断的ES-SCLC患者中，20.02%的患者ECOG体能状态评分（PS）≥2。荟萃分析结果表明，ECOG PS 对一线治疗后的生存结局无显著影响。与ECOG PS <2 的患者相比，ECOG PS ≥2 的患者在总生存期（OS）（风险比（HR）= 1.14，95%置信区间：0.80 - 1.63）或无进展生存期（PFS）（HR = 1.19，95%置信区间：0.88 - 1.62）方面无显著差异。亚组分析进一步显示，在接受一线免疫化疗的患者中，ECOG PS ≥2和 PS <2 亚组的OS（HR = 1.25，95%置信区间：0.77 - 2.03）和PFS（HR = 1.10，95%置信区间：0.78 - 1.54）也无显著差异。值得注意的是，在ECOG PS ≥2 亚组中，免疫化疗相较于单纯化疗具有显著的生存优势，OS HR 为 0.64（95%置信区间：0.47 - 0.87），PFS HR 为 0.44（95%置信区间：0.28 - 0.68），表明其具有短期和长期生存获益。
结论：
该研究结果表明，在广泛期小细胞肺癌患者中，诊断时的基线 ECOG 体能状态评分对长期预后并无显著影响，体能状态评分为 2 分及以上的患者也能从一线免疫化疗中获得显著的生存获益。然而，纳入的大多数研究均为回顾性的真实世界研究，因此对结果的解读需谨慎。有必要开展大规模的前瞻性试验，纳入体能状态评分较差的患者，以全面评估一线免疫化疗在该人群中的疗效和安全性。
MRD动态监测在斯鲁利单抗联合化疗一线治疗广泛期小细胞肺癌的观察性研究
结果：
研究前瞻性入组初治广泛期小细胞肺癌患者，所有患者接受6周期斯鲁利单抗联合标准化疗后，继续斯鲁利单抗单药维持治疗。在不同时间点采集血浆ctDNA样本，采用覆盖2365个肺癌相关基因的高深度测序 panel（平均深度约30000×）分析MRD状态，并应用Kaplan-Meier法与log-rank检验进行生存分析。组织与血浆样本中前30基因对比显示，大多数基因（21/30）可在两者中共同检出，表明样本类型间一致性高。ORR为100%，DCR为100%（13/13）。持续MRD阳性组中位PFS为6.26个月，MRD清除组PFS未达到，P=0.043。
结论：
基于ctDNA 的微小残留病（MRD）检测是预测ES-SCLC预后的有前景的生物标志物。治疗期间的 MRD 清除预示着更长的PFS。ctDNA 监测比传统的影像学检查更能灵敏地检测病情进展，能更早地识别疾病的分子进展迹象。这些基于小样本群体的初步发现强调了需要通过更多数据进行进一步验证。
【参考文献】
[1] Issafras H, et al. Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy. PLoS One. 2021;16(12):e0257972.
[2] Hui E, et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science. 2017;355(6332):1428-1433.
[3] Patsoukis N, et al. Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. Commun Biol. 2020;3(1):128.
[4] Fenwick C, et al. Tumor suppression of novel anti-PD-1 antibodies mediated through CD28 costimulatory pathway. J Exp Med. 2019;216(7):1525-1541.
[5] Primavera E, et al. Computer-Aided Identification of Kinase-Targeted Small Molecules for Cancer: A Review on AKT Protein. Pharmaceuticals (Basel). 2023;16(7):993.
关于复宏汉霖
复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在全球获批上市9款产品，5个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，公司商业化生产基地已相继获得中国、欧盟和美国GMP认证。
复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖约50个分子，并全面推进基于自有抗PD-1单抗H药汉斯状®的肿瘤免疫联合疗法。截至目前，公司已获批上市产品包括全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状®（斯鲁利单抗，欧洲商品名：Hetronifly®）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、国内首个生物类似药汉利康®（利妥昔单抗）、以及地舒单抗生物类似药Bildyos®和Bilprevda®。公司亦同步就19个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。
Henlius Showcased 9 Study Findings on Serplulimab at 2025 WCLC with 3 Oral Presentations
On September 8, 2025, Henlius (2696.HK) announced that the latest findings of nine studies on its independently developed innovative anti-PD-1 monoclonal antibody(mAb), HANSIZHUANG (serplulimab, Hetronifly® in Europe), were presented at the 2025 World Conference on Lung Cancer (WCLC), with three of the studies delivered as oral presentations. Among the highlights, the latest results from the Phase III ASTRUM-002 study—evaluating serplulimab as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC)—were presented for the first time as an oral presentation at the conference. Serplulimab is the world’s first anti-PD-1 mAb approved for first-line treatment of small cell lung cancer and has been approved in nearly 40 countries and regions, including China, the UK, Germany, India, Indonesia, and Singapore, covering nearly half of the global population and accelerating global accessibility.
Henlius' self-developed innovative mAb has fully covered the first-line treatment of lung cancer. It has been approved for the treatment of squamous non-small cell lung cancer (sqNSCLC), non-squamous non-small cell lung cancer (nsqNSCLC), extensive stage small cell lung cancer (ES-SCLC), encompassing three lung cancer indications. In additon, the company is conducting a phase 3 international multi-centre clinical trial of serplulimab combined with chemotherapy and radiotherapy for limited-stage SCLC (LS-SCLC).
Due to its unique mode of recognition, serplulimab exhibits stronger PD-1 receptor endocytosis, resulting in reduction of PD-1 receptors retained on the surface of T cells[1], leading to faster and stronger immune activation effects. The results showed that, serplulimab reduced the recruitment of immune co-stimulatory receptor CD28 by PD-1, thereby decreasing the dephosphorylation of CD28 mediated by phosphatase SHP2 and retaining the signal transmitted by CD28[2-4]. Further downstream the signalling pathway, the activity of protein kinase AKT was enhanced[5], thereby promoting sustained activation of T cells.
Significantly prolongs PFS in nsqNSCLC patients, with clear benefits for brain metastasis
At this year’s WCLC, the results of the Phase 3 ASTRUM-002 study were orally presented by its leading PI, Professor Yuankai Shi of the Cancer Hospital, Chinese Academy of Medical Sciences, for the first time. The study results showed that the median progression-free survival (mPFS) of the serplulimab combined chemotherapy group reached 11.0 months, , an improvement of 5.4 months compared to chemotherapy group, with a 45% reduction in the risk of disease progression.
The brain metastasis subgroup analysis showed that adding serplulimab to chemotherapy significantly improved mPFS (8.1 months vs. 4.1 months). In the treatment group that included bevacizumab, there was still a trend of benefit in mPFS (9.7 months vs. 8.1 months). Additionally, the findings of a Phase 2 IIT study (SUPER BRAIN) on serplulimab combined with bevacizumab and chemotherapy for the first-line treatment of nsqNSCLC with brain metastasis were also delivered as mini oral presentation in the conference. The data on the four-drug combination therapy for brain metastasis further validated the efficacy of serplulimab combined with bevacizumab and chemotherapy in the brain metastasis population as demonstrated in ASTRUM-002.
Title: ASTRUM-002: First-Line Serplulimab Plus Chemotherapy With or Without HLX04 in Advanced Nonsquamous Non-small Cell Lung Cancer
Study Design: This was a three arm, randomized, double-blind, multicenter, phase 3 study. Patients with locally advanced or metastatic nsqNSCLC without EGFR sensitizing mutations or ALK/ROS rearrangements and no prior systemic therapy were randomized 1:1:1 to receive serplulimab + HX04 + chemo (group A), serplulimab +chemo (group B), or chemo (croup C). Serplulimab and HLX04 were given every 3 weeks. The primary endpoint was the BICR-assessed progression-free survival (PFS) per the REClST version 1.1. Secondary endpoints included other efficacy endpoints and safety.
Results: From November 25, 2019 to June 15, 2023 (data cutoff date), 636 patients were randomized to group A (n=212), B (n=214), or C (n=210). The median follow-up duration was 23.4 (95% CI, 21.6-24.9), 23.1 (95% Cl, 21.4-25.6), and 23.0 (95% CI, 20.7-25.6) months for the respective groups. Median PFS was significantly prolonged in group B than in group C (11.0 months vs. 5.6 months; stratified HR= 0.55, 95% CI 0.43-0.69, P < 0.0001), meeting the superiority criterion specified in the protocol. A numerical benefit in PFS was observed for group A compared to group B (12.6 months vs.11.0 months, HR=0.86, 95% CI 0.67-1.11, P=0.2529). Overall survival was not mature. Other efficacy results are listed in Table 1. Treatment-related adverse events leading to death occurred in 10 (4.7%), 5 (2.3%), and 7 (3.3%) patients in the respective groups.
Conclusion: The addition of serplulimab to chemo provided significant longer PFS compared to chemo alone in patents with locally advanced or metastatic nsqNSCLC, while the combination of serplulimab, bevacizumab and chemo provided numerical improvements in PFS when compared to serplulimab and chemo. Both treatment regimens had manageable safety profiles.
Title: Phase II Trial of Serplulimab Plus Bevacizumab and Chemotherapy for Treatment-Naive Non-Squamous NSCLC with Brain Metastases(SUPER BRAIN)
Study Design: This single-arm phase 2 clinical trial enrolled patients with advanced non-squamous NSCLC with untreated BMs that were either asymptomatic or had symptoms controlled by dehydration therapy. Patients received serplulimab combined with bevacizumab, pemetrexed, and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab plus bevacizumab and pemetrexed until disease progression, unacceptable toxicity, or death, for up to two years. The primary endpoint was intracranial progression-free survival (iPFS). Intracranial outcomes were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1.
Results: The median iPFS was 13.1, with 6-month and 12-month iPFS rates of 91.3 and 67.1% respectively. The median sPFS was 13.3 months. Nine patients (22.5%) died due to PD, and the 12-month OS rate was 71.3% . The intracranial ORR was 84.6%, with a 64.1% extracranial ORR, demonstrating potent antitumor activity.
The most common grade ≥3 TRAEs included decreased white blood cell/neutrophil count, reduced platelet count, and abnormal liver function. No treatment-related deaths were reported.
Conclusion: Serplulimab plus bevacizumab and chemotherapy demonstrated promising intracerebral antitumor efficacy and a manageable safety profile for patients with non-squamous NSCLC with BMs in the first-line setting.
Full Coverage of LC first-line treatment, exploring therapeutic potential in a broader population
At the same time, several IIT study findings on serplulimab-based immunotherapies were also selected for multiple sessions, including oral presentations, poster tours, and poster presentations. These studies explored the therapeutic potential of immunotherapy in a wide range of populations, such as EGFR-TKI-Resistant or perioperative NSCLC lung cancer patients, and confirmed the efficacy of serplulimab in more sub-groups of ES-SCLC patients.
Title: Bevacizumab Plus Serplulimab and Chemotherapy for EGFR-TKI-Resistant Non-squamous Non-small-cell Lung Cancer: A Phase 2 Study
Results: This is a multicenter, single-arm phase 2 trial. 46 patients from nine centers across China were enrolled (aged 18-70 years with EGFRmut nsq-NSCLC, ECOG PS 0-1, documented disease progression after first- to third-generation EGFR-TKI therapy (≤2 lines), and no history of immunochemotherapy exposure). Eligible patients receive 4-6 cycles of HLX04 (7.5 mg/kg, day 1) plus HLX10 (300 mg, day 1), in combination with standard chemotherapy consisting of pemetrexed and carboplatin every 3 weeks, followed by maintenance therapy with HLX04 plus HLX10 and pemetrexed until progression, unacceptable toxicity, or up to 2 years (35 cycles). This study enrolled . The ORR was 47.8% (95% CI: 32.9-63.0%), achieving the predefined target of 45.0%. The median TTR and DoR were 1.5 months (95% CI: 1.4 - 2.8) and 6.2 months (95% CI: 5.3 - NR), respectively. Patients without brain metastases were more likely to achieve better efficacy (ORR: 52.4% vs. 44.0%; median PFS: 9.5 vs. 7.1 months). PFS showed no significant differences across prior therapy lines or EGFR-TKI regimen. The median TTR and DoR were 1.5 months (95% CI: 1.4 - 2.8) and 6.2 months (95% CI: 5.3 - NR), respectively. The incidence of any grade of AEs was 80.4% (37/46), and 17 patients (37.0%) had grade ≥3 AEs.
Conclusion: These findings indicated that a dose-reduced bevacizumab regimen combined with serplulimab and platinum-based doublet chemotherapy exhibited promising efficacy and manageable safety for patients with EGFR-TKI-resistant nsq-NSCLC.
Title: Serplulimab in Neoadjuvant Therapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Single-Arm Study
Results: This is a prospective, single-arm clinical study which enrolled 55 patients with stage II-IIIB (T4N2) NSCLC based on the AJCC 8th edition, whose tumors are assessed as resectable or potentially resectable. Patients received 3 cycles of neoadjuvant therapy consisting of serplulimab (300 mg) combined with chemotherapy. Radiographic assessment showed complete response (CR) in 2 patients. Partial response (PR) in 38 (90.5%), and stable disease (SD) in 2 (4.8%). The ORR was 95.2% (40/42). 87.5%(35/40) patients underwent thorascopic resection. The R0 resection rate was 100%. The MPR rate was 67.5% (27/40), and the pcr rate was 37.5% (15/40). 20 patients (36.4%, 20/55) experienced AEs, including 5 patients (9.1%, 5/55) with grade ≥3 AEs. 6 patients discontinued treatment due to AEs, but no surgical was delayed due to treatment-related toxicity. 1 patient developed a serious perioperative complication (bronchopleural fistula), which resolved after stent placement and conservative management.
Conclusion: Interim results suggest that serplulimab in combination with chemotherapy demonstrates promising efficacy and manageable safety as neoadjuvant therapy for patients with locally advanced NSCLC. These findings warrant confirmation with continued patient enrollment and longer follow-up.
Title: Multi-Cycle Low-Dose Radiotherapy Reshapes lmmunochemotherapy forES-SCLC: The SPUR Phase II Trial
Results: This is a Phase II, single-arm, multicenter study designed to evaluate the safety and efficacy of LDRT-concurrent cisplatin/carboplatin plus etoposide with Serplulimab in participants who have ES-SCLC and are chemotherapy-naïve for their extensive-stage disease. At data cut-off (July 31, 2025), the median follow-up was 17.9 months (range: 0.8-27.2). The confirmed objective response rate (ORR) was 84.8% (50/59; 95%CI: 73.0-92.8%), and DCR was 88.1% (52/59; 95% CI: 77.1-95.1%); The median DoR was 7.7 months (95% CI: 4.1-11.0). The median PFS was 7.3 months (95%CI: 5.9 – 11.6), with a 6-month PFS rate of 61.1% (95% CI: 50.0 – 74.9%), and 12-month PFS rate of 31.5% (95% CI: 21.5-46.0%). Patients without liver metastases experienced significantly longer PFS than those with liver metastases (median PFS: 10.7 vs. 4.4 months; log-rank P = 0.002). The OS data was not mature yet.
Conclusion: This study demonstrated a promising survival benefit and manageable toxicity of first-line serplulimab and chemotherapy combined with multi-cycle LDRT in ES-SCLC. Twelve patients (19.7%) are still on treatment, long-term and exploratory analysis results are warranted.
Title: First-Line Immunochemotherapy in ES-SCLC Patients with ECOG PS ≥2: Real-World Evidence from the ASTRUM-005R Trial
Results: ASTRUM-005R is a nationwide, real-world, observational study conducted in China to assess the safety and effectiveness of first-line serplulimab-based immunochemotherapy in patients with ES-SCLC. This subgroup analysis focused on patients with ECOG PS ≥2 to explore the feasibility and clinical outcomes in this population. A total of 75 patients with ECOG PS ≥2 were included in this analysis, accounting for 11.8% of the overall ASTRUM-005R cohort. Among them, 71 patients had PS 2 and 4 had PS 3. The median follow-up duration was 16.37 months (range, 1.90-23.60). Compared to patients with PS <2, poor performance status did not significantly affect rwPFS (HR = 1.15, P = 0.366). The median rwPFS for patients with PS ≥2 was 6.97 months (95% CI, 6.23-10.43), with a 1-year rwPFS rate of 26.62% (95% CI, 17.22-41.14). Similar to the overall cohort, baseline brain metastases had no significant impact on rwPFS (HR = 0.98, P = 0.953). However, patients with liver metastases had significantly shorter rwPFS than those without (4.93 vs. 10.30 months; HR = 1.95, P = 0.018). OS was poorer in patients with PS ≥2 compared to those with PS <2 (HR = 1.89, P < 0.001), with a median OS of 12.33 months (95% CI, 10.43-15.57). Again, brain metastases had no significant effect on OS (HR = 0.86, P = 0.640), while liver metastases were associated with inferior OS (9.67 vs. 14.03 months; HR = 3.01, P = 0.001). Among 74 patients with measurable disease and at least one post-treatment radiological evaluation, the ORR was 66.22% (95% CI, 54.28-76.81). Safety profiles in patients with ECOG PS ≥2 were generally consistent with those observed in the overall population. Adverse events (AEs) were reported in 20 patients (26.67%), and 15 patients experienced immune-related adverse events (irAEs), with 5 reporting grade ≥3 irAEs.
Conclusion: Our findings suggest that baseline ECOG PS at diagnosis does not significantly impact long-term prognosis in ES-SCLC patients, and those with ECOG PS ≥2 can also derive substantial survival benefits from first-line immunochemotherapy. However, most of the included studies were retrospective real-world studies, necessitating cautious interpretation of the results. Further large-scale prospective trials incorporating patients with poor ECOG PS are warranted to comprehensively assess the efficacy and safety of first-line immunochemotherapy in this population.
Title: Meta-Analysis of First-Line Immunochemotherapy in ES-SCLC: Does ECOG PS ≥2 Affect Survival Outcomes?
Results: This meta-analysis evaluates the survival benefits of first-line immunochemotherapy in ES-SCLC patients with ECOG PS ≥2. The pooled analysis estimated that 20.02% (95% CI 14.39-26.29) of newly diagnosed ES-SCLC patients had ECOG PS ≥2. Meta-analysis results demonstrated that ECOG PS did not significantly impact survival outcomes following first-line treatment. Compared to patients with ECOG PS <2, those with ECOG PS ≥2 exhibited no significant difference in OS (HR = 1.14, 95% CI: 0.80-1.63) or PFS (HR = 1.19, 95% CI: 0.88-1.62). Subgroup analysis further revealed that among patients receiving first-line immunochemotherapy, OS (HR = 1.25, 95% CI: 0.77-2.03) and PFS (HR = 1.10, 95% CI: 0.78-1.54) did not differ significantly between ECOG PS ≥2 and PS <2 subgroups. Notably, in the ECOG PS ≥2 subgroup, immunochemotherapy conferred a significant survival advantage compared to chemotherapy alone, with an OS HR of 0.64 (95% CI: 0.47-0.87) and a PFS HR of 0.44 (95% CI: 0.28-0.68), indicating both short- and long-term survival benefits.
Conclusion: Our findings suggest that baseline ECOG PS at diagnosis does not significantly impact long-term prognosis in ES-SCLC patients, and those with ECOG PS ≥2 can also derive substantial survival benefits from first-line immunochemotherapy. However, most of the included studies were retrospective real-world studies, necessitating cautious interpretation of the results. Further large-scale prospective trials incorporating patients with poor ECOG PS are warranted to comprehensively assess the efficacy and safety of first-line immunochemotherapy in this population."
Title: Minimal Residual Disease Dynamic Monitoring in First-Line Serplulimab Plus Chemotherapy in Treatment of Extensive-Stage Small Cell Lung Cancer
Results: This study prospectively enrolled previously untreated ES-SCLC patients. All patients received 6 cycles of standard chemotherapy combined with serplulimab, followed by serplulimab monotherapy maintenance. Plasma ctDNA samples were collected at multiple time points, including the baseline, after 2 and 6 cycles of chemo-immunotherapy, at 6 months post-chemotherapy cessation, and upon tumor progression. The MRD status was identified by a next-generation sequencing panel covering 2365 lung cancer-relevant genes with an average sequencing depth of approximately 30000×. Kaplan-Meier curves and log-rank tests were performed in survival analyses. A comparison of the top 30 genes in tissue and plasma. Most genes detected in tissue (21/30) were also detectable in plasma, demonstrating a high degree of consistency between the two sample types. ORR：100% DCR：100% （13/13). Persistent MRD+group PFS 6.26m；MRD clearance group PFS NA，P = 0.043；
Conclusion: tDNA-based MRD detection represents a promising biomarker for predicting prognosis in ES-SCLC. MRD clearance during treatment predicts better PFS. ctDNA monitoring is more sensitive than conventional imaging for detecting progression, identifying molecular signs of disease progression months earlier. These preliminary findings, based on a small cohort, highlight the need for further validation with expanded data.
About Henlius
Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 9 products have been approved for marketing worldwide, and 5 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP.
Henlius has pro-actively built a diversified and high-quality product pipeline covering about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include HANSIZHUANG (serplulimab, trade name: Hetronifly® in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANLIKANG (rituximab), the first China-developed biosimilar, and denosumab Bildyos® and Bilprevda®. What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.
联系方式
媒体：PR@Henlius.com
投资者：IR@Henlius.com
喜欢本文内容
点击下方按钮·分享 ·收藏 ·点赞 ·在看
