WCLC 2025 | 复宏汉霖创新型抗PD-1单抗H药3项口头报告，9项研究结果公布

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。 

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。

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。

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.

媒体：PR@Henlius.com

投资者：IR@Henlius.com