非鳞NSCLC中位OS突破两年！复宏汉霖H药多项研究结果在ESMO 2025大会发布

聚焦肺癌和消化道肿瘤等高发实体肿瘤，H药 汉斯状^®不断取得突破性进展，为全球首个获批用于一线治疗小细胞肺癌的抗PD-1单抗，已在中国、英国、德国、新加坡、印度等近40个国家和地区获批上市，覆盖全球近半数人口。2025年10月，H药用于胃癌围手术期的III期临床研究（ASTRUM-006）期中分析达到了主要研究终点无事件生存期（EFS），成为全球首个胃癌围术期以免疫单药取代术后辅助化疗的治疗方案，支持提前申报上市。截至目前，H药已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）、食管鳞状细胞癌（ESCC）和非鳞状非小细胞肺癌（nsqNSCLC），并在美国和日本同步开展ES-SCLC的桥接试验。

在肺癌领域，H药目前已全面覆盖肺癌一线治疗。基于H药联合化疗一线治疗晚期nsqNSCLC的III期临床（ASTRUM-002）研究结果，H药于2024年12月在中国获批用于该适应症。本次ESMO 2025大会上，ASTRUM-002牵头主要研究者、中国医学科学院肿瘤医院石远凯教授口头报告了截至2025年8月7日的最终分析结果，首次正式公布关键次要终点OS数据，进一步验证了该方案为晚期nsqNSCLC患者带来的长期生存获益。此前该研究已在WCLC 2025大会上发布了截至2023年6月15日的数据，包含主要终点PFS。

最终分析显示，与化疗相比，斯鲁利单抗联合化疗显著改善OS，并持续显示出显著的PFS获益。H药联合化疗组mOS达26.8个月（95% CI：21.2–30.9），突破两年大关，而化疗组为20.3个月（95% CI：16.2–24.6），死亡风险显著降低（HR=0.66，95% CI：0.52–0.83，p=0.0004）。化疗组中共有79例（37.6%）患者交叉接受了斯鲁利单抗联合HLX04治疗。经两阶段模型校正后，化疗组中位总生存期为14.2个月（95%置信区间：11.9-17.0），斯鲁利单抗联合化疗组较校正后的化疗组风险比更具优势（HR=0.53，95% CI：0.42-0.68，p<0.0001）。此次大会上更新的PFS数据显示，斯鲁利单抗联合化疗组中位PFS（mPFS）为11.0个月，较化疗组延长5.3个月，疾病进展风险下降46%。尤其在接受斯鲁利单抗联合化疗治疗的TPS≥50%的亚组中，PFS和OS均获益显著，mOS达45.4个月，mPFS为12.1个月，疾病进展风险降低64%。

研究证实，斯鲁利单抗联合化疗可为局部晚期或转移性nsqNSCLC患者带来显著生存获益，其卓越的长期疗效与可控的安全性，为患者提供了一线治疗新选择。

在消化道肿瘤领域，H药也迎来了关键临床突破。2025年10月，H药胃癌围手术期的III期临床ASTRUM-006研究期中分析达到了主要研究终点EFS，成为全球首个胃癌围术期以免疫单药取代术后辅助化疗的治疗方案，有望重塑胃癌围手术治疗新标准，为早期胃癌患者带来治愈希望。期中分析结果显示，与安慰剂联合化疗相比，汉斯状^®联合化疗显著改善EFS，病理完全缓解（pCR）率是对照组3倍多，患者复发风险明显降低。同时，该治疗方案安全性良好，未发现新的安全性信号。基于这一积极结果，建议提前申报上市。

此外，H药联合贝伐珠单抗联合化疗用于一线治疗转移性结直肠癌（mCRC）患者的国际多中心临床研究（ASTRUM-015）III期研究也并已完成患者入组。多项探索H药联合化疗新辅助治疗局部进展期胃或食管胃结合部腺癌、中低位直肠癌以及联合贝伐珠单抗一线治疗晚期胰腺癌的IIT研究也在本次大会上发布更新数据。

本次大会上公布的H药相关研究具体信息如下：

mOS in nsqNSCLC Exceeds Two Years! Henlius Announces Latest Results for Serplulimab at ESMO 2025

On October 21, 2025, Henlius (2696.HK) announced that the latest results of multiple studies in the fields of lung cancer and gastrointestinal tumours for its self-developed innovative anti-PD-1 mAb HANSIZHUANG (serplulimab, Hetronifly^® in Europe) were released at the 2025 European Society for Medical Oncology Annual Meeting (ESMO 2025). Among them, the final analysis results of the Phase III clinical study (ASTRUM-002) of serplulimab for first-line treatment of advanced non-squamous non-small cell lung cancer (nsqNSCLC) were selected for the conference's Late-breaking Abstract (LBA) and the overall survival (OS) data was orally presented for the first time. The final analysis results showed that the median overall survival (mOS) for the serplulimab plus chemotherapy group reached 26.8 months, successfully surpassing the two-year mark.

Focusing on high-incidence solid tumours such as lung and gastrointestinal cancers, serplulimab has continuously achieved breakthrough progress. It 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, Singapore and India, covering nearly half of the global population. In October 2025, the phase 3 clinical trial of HANSIZHUANG for perioperative gastric cancer treatment met its EFS primary endpoint, becoming world-first regimen in gastric cancer that replaces adjuvant chemotherapy with mono-immunotherapy in the perioperative setting, supporting an early New Drug Application (NDA) submission. To date, serplulimab has been approved for the treatment of squamous NSCLC (sqNSCLC), extensive-stage SCLC (ES-SCLC), esophageal squamous cell carcinoma (ESCC), and non-squamous NSCLC (nsqNSCLC). Bridging studies for ES-SCLC are currently underway in the United States and Japan.

Comprehensive coverage for first-line lung cancer treatment, long-term survival exceeding two years for advanced nsqNSCLC

In the field of lung cancer, serplulimab has fully covered the first-line lung cancer treatment. Based on the results of the Phase III clinical study (ASTRUM-002) for serplulimab plus chemotherapy in first-line treatment of advanced nsqNSCLC, serplulimab was approved for this indication in China in December 2024. At the ESMO 2025 conference, the leading principal investigator of ASTRUM-002, Professor Yuankai Shi from Cancer Hospital, Chinese Academy of Medical Sciences, orally presented the final analysis results as of August 7, 2025, formally announcing the key secondary endpoint OS data for the first time, further validating the long-term survival benefits brought by this regimen to patients with advanced nsqNSCLC. Previously, this study had released data (as of June 15, 2023), including results of the primary endpoint PFS, at the WCLC 2025 conference.

The study results confirmed that serplulimab plus chemotherapy can confer significant survival benefits to patients with treatment-naïve, locally advanced or metastatic nsqNSCLC. Its outstanding long-term efficacy and controllable safety provide patients with an alternative first-line treatment option.

Breakthroughs in gastrointestinal tumours to address unmet clinical needs

In the field of gastrointestinal tumours, serplulimab has also achieved critical clinical breakthroughs. In October 2025, the Phase 3 clinical study ASTRUM-006 for perioperative gastric cancer reached the primary study endpoint EFS, becoming the world's first treatment regimen for perioperative gastric cancer to replace adjuvant chemotherapy with mono-immunotherapy in the perioperative setting, potentially reshaping the new standard for perioperative gastric cancer treatment and bringing hope for a cure to early gastric cancer patients. The interim analysis results showed that compared with placebo plus chemotherapy, HANSIZHUANG plus chemotherapy significantly prolonged EFS and achieved a more than threefold higher pathological complete response (pCR) rate compared with the control arm, with a significant reduction in the risk of recurrence. Furthermore, the combination regimen demonstrated a favorable safety profile, with no new safety signals identified. Based on this positive outcome, the IDMC has recommended an early NDA submission.

Additionally, the international multicenter Phase 3 clinical study (ASTRUM-015) of serplulimab combined with bevacizumab and chemotherapy for first-line treatment of metastatic colorectal cancer (mCRC) patients has completed patient enrollment. Several exploratory IIT studies of serplulimab plus chemotherapy for neoadjuvant treatment of locally advanced gastric or gastroesophageal junction adenocarcinoma, mid-low rectal cancer, and first-line treatment of advanced pancreatic cancer when combined with bevacizumab were also updated at this conference.

Specific information on studies of serplulimab at this conference is as follows:

Title: Final Analysis of First-Line Serplulimab Plus Chemotherapy With or Without HLX04 in Advanced Nonsquamous Non-small Cell Lung Cancer: the ASTRUM-002 Phase 3 Study

Study design: This was a three-arm, randomised, double-blind, multicentre, phase 3 study. Patients with locally advanced or metastatic nsqNSCLC without EGFR sensitizing mutations or ALK/ROS1 rearrangements and no prior systemic therapy were randomised 1:1:1 to receive serplulimab + HLX04 + chemotherapy (chemo) (group A), serplulimab + chemo (group B), or chemo (group C). The primary endpoint was the BICR-assessed PFS per RECIST version 1.1. The key secondary endpoint was OS.

Results:  Between Nov. 25, 2019 to Jun. 15, 2022, 636 patients were enrolled across 72 hospitals in China and randomised to group A (n=212), B (n=214), or C (n=210), with a median follow-up duration of 48.4 (95% CI 45.9–49.9), 45.4 (95% CI 43.3–49.1), and 45.7 (95% CI 43.6–51.7) months, respectively. Median OS was 23.7 months (95% CI 20.5–27.5), 26.8 months (95% CI 21.2–30.9), and 20.3 months (95% CI 16.2–24.6), in group A, B, and C, respectively. A significant reduction in risk of death for group B compared to C was observed (HR=0.66, 95% CI 0.52–0.83, p=0.0004), while no statistical difference was observed for group A compared to B (HR=1.12, p=0.3628). By the time of the final analysis, 79 (37.6%) patients in group C had crossed over to serplulimab plus HLX04 treatment. Median OS in group C as adjusted by the two-stage model was 14.2 months (95% CI: 11.9–17.0), resulting in an adjusted HR of 0.53 (95% CI: 0.42–0.68, p<0.0001) for group B versus group C. Subgroup analysis of median OS was consistent with that of the primary findings. Median PFS and tumour response continued to be improved for group B compared to group C. Treatment-related adverse events leading to death occurred in 10 (4.7%), 5 (2.3%), and 7 (3.3%) patients, in group A, B, and C, respectively.

Conclusion: The combination of serplulimab to chemo significantly prolonged OS and continued to confer significant PFS and clinical benefits compared to chemo alone, making it a promising first-line treatment option for patients with locally advanced or metastatic nsqNSCLC. The addition of HLX04 to serplulimab and chemo did not lead to a further improvement. Both investigated treatment regimens had manageable safety profiles.

Title: Surgery versus radiotherapy after induction therapy with serplulimab combined with chemotherapy for unresectable stage IIIB-IIIC non-small cell lung cancer: a randomized controlled, open-label, phase 2 trial

Results: One hundred patients were enrolled, and the median follow-up time was 20.3 months by the data cutoff date (April 28, 2025). Sixty-six and 34 patients were diagnosed with stage IIIB and IIIC disease, respectively. Fifty patients were randomly assigned to either the surgery group (n = 23) or the radiotherapy group (n = 27). The percentage of squamous carcinomas, adenocarcinomas, and NSCLC not otherwise specified were 70.0%, 16.0%, and 14.0%, respectively. In the entire enrolled patients, ORR was 75.0%. In total, 33 patients received surgery (all achieving R0 resection) after 1-4 cycles of induction chemoimmunotherapy, and the MPR rate was 66.7% (22/33). The median EFS and OS for the entire study cohort were 17.7 months and not reached, respectively. Among randomized patients, the hazard ratio (HR) for surgery versus radiotherapy in EFS in the intention-to-treat and per-protocol populations were 0.35 (95% CI: 0.13-0.91, P = 0.025) and 0.21 (95% CI: 0.07-0.59, P = 0.003), respectively. While, no significant difference in OS was observed. SAE and grade 3-5 treatment-related adverse event rates in induction therapy phase were 12.0% and 58.0%, respectively.

Conclusion: Induction therapy with serplulimab and chemotherapy converted half of the patients with unresectable stage IIIB–IIIC NSCLC to resectable disease and demonstrated promising survival outcomes. Among patients whose disease was converted to resectable, those who underwent surgery showed a trend toward improved event-free survival (EFS) compared with those who received radiotherapy. Induction therapy with serplulimab and chemotherapy, followed by either surgery or radiotherapy, revealed no new safety signals.

Title: Total neoadjuvant chemotherapy plus PD-1 antibody in locally advanced gastric or gastro-esophageal junction adenocarcinoma: A proof-of-concept, phase 2 trial

Results: Between Mar 2023 and Jan 2024, 30 patients were enrolled. All patients received at least one cycle of assigned neoadjuvant treatment, and the median cycles were seven (IQR: 6-8). Among the 25 patients who underwent surgery, eight patients achieved pCR. A total of 3 patients who completed total neoadjuvant serplulimab and chemotherapy and underwent at least 12 months of follow-up achieved a cCR. Therefore, the pCR/12m-cCR rate was 36.7% (11/30, 95% CI: 19.9%-56.1%).

Conclusion: Total neoadjuvant chemotherapy plus PD-1 antibody might be a promising option for patients with locally advanced gastric or GEJ cancer.

Title: Serplulimab Combined with CapeOX and Celecoxib as Neoadjuvant Therapy for Proficient Mismatch Repair Locally Advanced Mid-to-Low Rectal Cancer (SCAR)

Results: As of Jan 2025, 22 patients were enrolled, with a median age of 60.5 years, 86.4% being male. 16 achieved PR or CR before surgery, with ORR of 72.7% (16/22; 95% CI: 49.8-89.3%). 18 (81.8%) patients have received radical surgery. R0 resection rate was 100%. After pathological evaluation, 4 patients achieved PCR(22.2%).No new safety signal was discovered during perioperative period.ScRNA-seq analysis revealed increased CD8+ T cell levels in PR and CR patients

Conclusion: The combination of serplulimab, CapeOX, and celecoxib as neoadjuvant therapy for locally advanced mid-to-low rectal cancer demonstrated primary efficacy and safety.

Title: First-line Serplulimab and Bevacizumab Combined with Nab-Paclitaxel/Gemcitabine Followed by mFOLFOX in Advanced Pancreatic Cancer: A Phase II Trial

Results: Among the 37 patients analyzed, the average age was 62 years. Patients had an adequate nutritional and performance status, with a mean BMI of 21.6 kg/m2. Distant organ metastases were present in 34 patients (91.9%), with the liver being the most common site (n=26, 70.3%).The confirmed ORR was 67.6% (95% CI, 49.5-82.6).1 patient had a complete response (CR).The median PFS was 10.5 months (95% CI, 9.7-not reached). 6-month PFS rate of 80.0% (95% CI, 65.5-97.7). The OS remains immature.The median duration of response (DOR) was 9.3 months, The median time to response (TTR) was 1.5 months. grade ≥3 TRAEs occurring in 46.0% of patients.Hematologic toxicities were the most common treatment-emergent adverse events. No fatal AEs were observed.

Conclusion: First-line serplulimab and bevacizumab biosimilar combined with nab-P/Gem-mFOLFOX demonstrates clinical feasibility and promising preliminary outcomes in advanced PC. Further follow-up is required to confirm the survival benefits, and following analyses are needed to explore the mechanisms underlying the efficacy of this novel regimen.

媒体：PR@Henlius.com

投资者：IR@Henlius.com