ESMO Asia | 复宏汉霖H药多元领域研究公布，验证广泛临床价值

H药是全球首个一线治疗小细胞肺癌的抗PD-1单抗，也是全球唯一胃癌围手术期III期注册研究成功的抗PD-1单抗。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（nsNSCLC) 适应症，在中国、英国、德国、新加坡、印度等40多个国家获批上市，覆盖全球近半数人口。凭借其差异化的机制，H药在多种实体瘤的治疗中展现出独特优势，在肺癌和胃癌领域皆斩获全球突破性进展。该药物不仅具备更强的PD-1内吞作用，可减少T细胞表面PD-1受体^[1]，实现快速、强效的免疫激活；还能减少PD-1对共刺激分子CD28的募集，从而更大程度保留CD28信号传导^[2-4]，增强下游AKT蛋白活性^[5]，促进T细胞持续活化。

在肺癌领域，H药目前已全面覆盖肺癌一线治疗。除了已获批的sqNSCLC、ES-SCLC和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，并在美国和日本同步开展ES-SCLC的桥接试验，其美国头对头桥接试验已完成患者入组。在消化道肿瘤领域，公司持续深化H药的临床探索，H药联合化疗用于新辅助/辅助治疗胃癌III期临床研究取得成功，并已被CDE纳入突破性治疗品种名单，作为全球首个胃癌术后免化疗方案，有望加速惠及患者。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III期临床研究（ASTRUM-015）也于全球多个国家同步推进中。

在本次ESMO Asia大会上，H药公布了前瞻性IIT研究在治疗MSS型转移性结直肠癌（mCRC）和局晚期头颈部鳞状细胞癌（HNSCC）的最新结果，显示了免疫联合疗法的初步疗效和带来的潜在临床获益。此外，大会也报告了H药在HER2阳性晚期胃癌中的IIT研究进展。H药相关真实世界研究数据则进一步验证了其一线治疗晚期鳞状非小细胞肺癌的疗效，并探索了其用于新辅助治疗局晚期非小细胞肺癌和用于治疗宫颈癌的前景。

Henlius Unveils Multi-Disciplinary Research on Serplulimab at ESMO Asia, Demonstrating Broad Clinical Value

The 2025 European Society for Medical Oncology Asia (ESMO Asia 2025) Congress were held in Singapore from December 5–7, 2025. At this conference, latest results from seven studies on Henlius’ innovative anti-PD-1 monoclonal antibody, HANSIZHUANG (serplulimab, Hetronifly^® in Europe) were released. These studies span lung cancer, gastrointestinal tumors, squamous cell carcinoma, and gynecological cancer, underscoring the extensive clinical value of serplulimab.

Serplulimab is the world’s first anti-PD-1 monoclonal antibody(mAb) approved for the first-line treatment of small cell lung cancer (SCLC), and the only anti-PD-1 mAb to have succeeded in a Phase 3 perioperative registration study in gastric cancer. 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). It has been approved in over 40 countries and regions including China, the U.K., Germany, Singapore and India, covering nearly half of the global population and accelerating global accessibility. Serplulimab demonstrates unique advantages in treating various solid tumors via its differentiated mechanism, especially achieving groundbreaking progress in both lung and gastric cancers. The drug not only induces stronger PD-1 internalization—reducing PD-1 receptor presence on T cells for rapid and potent immune activation ^[1]—but also minimizes PD-1-mediated recruitment of the co-stimulatory molecule CD28, thereby preserving CD28 signaling ^[2-4], enhancing downstream AKT activity ^[5], and promoting sustained T-cell activation.

In lung cancer, serplulimab has covered the full range of first-line treatment. Beyond its three approved indications (sqNSCLC, ES-SCLC, nsqNSCLC), Henlius is conducting a global, multicenter Phase 3 trial of serplulimab plus chemotherapy and radiotherapy for first-line treatment of limited-stage SCLC (LS-SCLC).  Additionally, bridging studies for ES-SCLC are underway in both the U.S. and Japan, with patient enrollment for the head-to-head bridging study in the U.S. already completed. In the field of gastrointestinal cancers, the company continues to deepen its clinical exploration of serplulimab. In addition to the approved indication for ESCC, the phase 3 clinical trial of serplulimab plus chemotherapy as neoadjuvant/adjuvant therapy for gastric cancer has met its primary endpoint. As the world-first regimen in gastric cancer that replaces adjuvant chemotherapy with mono-immunotherapy in the perioperative setting, serplulimab has been granted breakthrough therapy designation by the Center for Drug Evaluation (CDE) of China. Besides, an international, multicenter Phase 3 trial (ASTRUM-015) of serplulimab in combination with bevacizumab and chemotherapy as first-line therapy for metastatic colorectal cancer (mCRC) is being simultaneously advanced in multiple countries worldwide.

At this ESMO Asia conference, latest results from prospective IIT studies on serplulimab in treating MSS-type metastatic colorectal cancer (mCRC) and locally advanced head and neck squamous cell carcinoma (HNSCC) have been released, demonstrating preliminary efficacy and potential clinical benefits of immunotherapy combination therapy. Besides, latest results from IIT studies assessing serplulimab in HER2-positive advanced gastric cancer were also published at the conference. Real-world research data related to serplulimab further validated its efficacy in first-line treatment of advanced sqNSCLC and explored its prospects for neoadjuvant therapy in locally advanced NSCLC and treatment of cervical cancer.

#Squamous Cell Carcinoma

Title: Induction Serplulimab and Cetuximab Combined with Chemotherapy Followed by Radiotherapy for Unresectable Locally Advanced HNSCC: A Single-arm, Prospective, Phase II Study

Results: This single-arm, prospective, phase II study enrolled patients with confirmed unresectable LA-HNSCC (excluding nasopharyngeal carcinoma). Patients received serplulimab (4.5 mg/kg, Q3W) + cetuximab (400 mg/m2 loading, followed by 250 mg/m2, QW) + liposomal paclitaxel (135 mg/m2, D1) + cisplatin (75 mg/m2, Q3W), for 3 weeks per cycle, with 2 total treatment cycles. Definitive radiotherapy was administered following the induction therapy. From Sep 2024 to Jun 2025, this study enrolled 9 patients with a median age of 67 years (range, 54-72), with 88.9% having a history of smoking. The most common primary tumor site was the hypopharynx (44.4%). After two cycles of induction therapy, both the ORR and DCR reached 100.0% (95% CI 66.4–100.0), including five patients (55.6%) who achieved a complete response (CR), and no cases of progressive disease (PD) were observed. Following evaluation, 77.8% of patients proceeded to receive radical radiotherapy. The most frequently observed grade ≥3 treatment-related adverse event (TRAE) was myelosuppression, occurring in 33.3% of patients. No unexpected or treatment-related fatal adverse events were observed, and the survival data remain immature at this stage.

Conclusion: In patients with unresectable LA-HNSCC, this induction regimen showed preliminary efficacy and manageable toxicity. Further follow-up is required to confirm the survival benefit.

#Gastrointestinal Tumors

Title: A Multicenter Randomized Trial of Serplulimab After mFOLFOX6 and HLX04 Induction in First-Line Treatment of MSS Metastatic Colorectal Cancer

Results: This prospective, multicenter, randomized controlled trial enrolled treatment-naïve patients(pts) with MSS unresectable mCRC. Pts were randomized 1:1 to receive mFOLFOX6 plus HLX04 (bevacizumab biosimilar), with or without the addition of serplulimab (PD-1 inhibitor) after two induction cycles. Pts who achieved disease control after 4-6 months treatment would enter maintenance stage. As of Aug 1st, 2025, 19 pts had been enrolled, including 10 pts receiving serplulimab. Pts in serplulimab arm had a higher baseline tumor burden versus control arm.  Despite this, the serplulimab arm achieved better efficacy in PFS (7.2 months vs 6.1 months), and it also showed a higher 6-month PFS rate (87.5% vs 59.3%); Additionally, the serplulimab arm achieved better efficacy in ORR (90% vs 77.7%), and DCR (90% vs 77.7%).Multiplex immunohistochemistry (mIHC) analysis also revealed a post-treatment decrease in CD4 + Treg cells（CD3+CD4+Foxp3+）.

Conclusion: This preliminary analysis suggests that first-line induction with mFOLFOX6 and HLX04, followed by the addition of serplulimab, may provide clinical benefit in MSS mCRC. mIHC data offers unique insights of tumor microenvironment.

Title: Updated outcome and ctDNA Profiling in Advanced HER2+ Gastric Cancer Patients Treated with DOS plus Serplulimab and Trastuzumab: A Phase II Multicenter Trial 

Results:This Phase II trial (NCT05311189) enrolled 40 unresectable/metastatic HER2+ gastric cancer patients (July 2022–September 2024) treated with intensive chemotherapy plus PD-1 and HER2 blockade. Among the 37 evaluable patients (median follow-up: 12.57 months(m)), the median progression-free survival (PFS) was 15.7 months (95% CI: 10.2 m to not reached). Among those with blood samples, 14 responders (Durable Clinical Benefit, DCB) and 14 non-responders(Non-durable Benefit, NDB) were stratified by a 12-month response duration cutoff. Overall, reduction of TGAs (SNVs and ERBB2 CN) , tumor fraction (TF), mutant allele frequency (MSAF), and blood-based tumor mutation burden (bTMB) were observed in C2D1 in plasma from enrolled patients.

Conclusion: DOS with plus S and T displayed sustained anti-tumor activity. ctDNA dynamics, especially blood ERBB2 CN hold substantial clinical utility for evaluating clinical outcomes in advanced HER2+ gastric cancer.

Title: Identification of Potential Immune Biomarkers associating to Clinical Benefit from Intensive Chemotherapy Combined with Serplulimab and Trastuzumab in Advanced HER2+ Gastric Cancer: A Post-hoc Analysis of the ASTRUM Study

Results: 40 pts enrolled (Jul 2022 – Sep 2024) received S (4.5 mg/kg Q3W), T (8 mg/kg → 6 mg/kg Q3W), and DOS chemo (oxaliplatin, docetaxel, S-1). Durable Clinical Benefit(DCB, n=16) and Non-durable Benefit(NDB, n=15) were defined by ≥ 12-month response. DCB tumors showed upregulation of CCL19/21, CD19/79, CXCL9/11, and CD28, indicating an immune-active profile. Pathway enrichment revealed B/T-cell activation, IFN-γ response, and antigen presentation. CD8⁺ T cells, B cells, TIS, and TLS were significantly increased and correlated with clinical benefit.

Conclusion: Integrated tumour and circulating immune signatures forecast durable efficacy of treatment. baseline immune biomarkers serve as putatively predictive biomarkers for clinical benefit.

#Lung Cancer

Title: Real-World Study of Serplulimab as First-Line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer

Results: We included patients with advanced sqNSCLC diagnosed via pathological or cytological examination and ineligible for surgery or radiotherapy. These patients received first-line treatment with serplulimab at the First Affiliated Hospital of Nanchang University between 2022 and 2024. All patients completed at least two cycles of serplulimab treatment. A total of 46 patients with advanced sqNSCLC were enrolled, including 27 with stage III and 19 with stage IV disease. The median age was 67 years (range: 41–86), and the median follow-up duration was 12 months (range: 1.47–24.63). Disease progression occurred in 21 patients (21/46, 45.65%), with a median PFS of 11.0 months (95% CI, 10.00–NR). The 1-year and 2-year PFS rates were 48.21% (95% CI, 33.66–69.06) and 27.39% (95% CI, 12.53–59.9), respectively. No statistically significant factors influencing PFS were identified in subgroup analyses. Among the treated patients, 27 achieved partial response (PR), resulting in an ORR of 58.70% (95% CI, 43.23–73.00). 1-year OS rate was 85.21% (95% CI, 73.75–98.46). AEs were reported in 22 patients (22/46, 47.83%), with no treatment-related deaths observed.

Conclusion: In this real-world study, serplulimab exhibited remarkable efficacy and a well-tolerated safety profile, supporting its use as a highly effective first-line immunotherapy option for advanced sqNSCLC.

Title: Efficacy and Safety of Neoadjuvant Serplulimab in Locally Advanced Driver Gene-Negative NSCLC: A Multicenter Real-World Study

Results: This prospective study enrolled patients with histologically confirmed, locally advanced NSCLC and no actionable genomic alterations. Patients received at least 1 cycle of neoadjuvant serplulimab (300 mg, Q3W) plus platinum-based chemotherapy, followed by definitive surgery. From Jan 2022 to Dec 2024, 27 patients (median age, 64 years) were enrolled, including 81.5% (22/27) with stage III disease. Among these patients, R0 resection was achieved in 92.6% (25/27). Pathological assessment revealed an MPR rate of 74.1% (20/27) and a pCR rate of 33.3% (9/27). Radiographically, 2 complete responses (CR) and 20 partial responses (PR) were observed, yielding an ORR of 81.5% (22/27; 95% CI, 61.9–93.7%) and a DCR of 96.3% (26/27; 95% CI, 81.0–99.9%). Exploratory biomarker analysis indicated that MPR was associated with higher baseline lymphocyte counts (P=0.003) and lower post-neoadjuvant neutrophil-to-lymphocyte ratio (NLR;P=0.035). At a median follow-up of 9.1 months (range 2.9–24.7), 4 EFS events occurred (including 1 death). Treatment-related adverse events (TRAEs) occurred in 37.0% (10/27), with grade ≥3 TRAEs in 7.4% (2/27).

Conclusion: Neoadjuvant serplulimab-chemotherapy demonstrated promising efficacy and manageable toxicity in real-world locally advanced NSCLC. Survival outcomes require longer follow-up to assess clinical benefit.

#Gynaecological Cancer

Title: Serplulimab in Advanced, Recurrent, or Metastatic Cervical Cancer: A Prospective Multicenter Real-World Study

Results: Eligible patients (aged ≥18 years) with advanced, recurrent, or metastatic cervical cancer were treated with serplulimab as monotherapy or in combination with other therapies in the post-initial settings. A total of 33 patients with advanced, recurrent, or metastatic cervical cancer were enrolled, with a median age of 60 years. Among the 27 patients evaluable for tumor response, two achieved a complete response (CR), and 15 achieved a partial response (PR), resulting in an ORR of 63.0% (95% CI, 42.4–80.6%) and a DCR of 92.6% (95%CI, 75.7–99.1%). PFS events occurred in 16 patients, with a median PFS of 8.6 months (95% CI, 7.0–NR). In multiple subgroup analyses, including comparisons between immunotherapy alone and immunotherapy combinations, no significant differences in PFS were observed. However, the addition of anti-angiogenic therapy to immunochemotherapy prolonged the median PFS by 2.5 months compared to regimens without anti-angiogenic agents (11.6 vs. 9.1 months). During the study period, two deaths were reported. A total of 23 patients (69.7%) experienced any grade adverse events (AEs), and three patients (9.1%) reported grade ≥ 3 treatment-related AEs. The incidence of AEs was lower in the immunotherapy monotherapy group compared to the combination immunotherapy group (60.0% vs. 77.8%).

Conclusion: Serplulimab demonstrated significant efficacy and a manageable safety profile in patients with advanced, recurrent, or metastatic cervical cancer. The absence of significant differences in efficacy observed in the subgroup analysis further indicates that serplulimab is a promising treatment option for patients with advanced, recurrent, or metastatic cervical cancer in the post-initial settings.

媒体：PR@Henlius.com

投资者：IR@Henlius.com