Shanghai Henlius Biotech announced comprehensive clinical data for serplulimab (HANSIZHUANG), its anti-PD-1 monoclonal antibody, at the 2025 American Society of Clinical Oncology Annual Meeting. The presentations encompassed results from over ten studies spanning lung and gastrointestinal cancers, reinforcing the drug's therapeutic potential across multiple oncology indications.
Serplulimab represents the first anti-PD-1 monoclonal antibody approved for first-line treatment of small cell lung cancer and has received regulatory approval in over 30 countries and regions, including China, Europe, and Southeast Asia. The company has initiated more than 10 clinical trials investigating immuno-oncology combination therapies across various indications, with over 4,900 subjects enrolled globally.
Landmark Lung Cancer Results Demonstrate Long-term Survival Benefits
The phase 3 ASTRUM-005 study, led by Professor Ying Cheng from Jilin Cancer Hospital, provided definitive evidence of serplulimab's efficacy in extensive-stage small cell lung cancer. The international trial randomized 585 patients between September 2019 and April 2021, with 389 patients receiving serplulimab at 4.5 mg/kg plus chemotherapy and 196 patients receiving placebo plus chemotherapy.
Final analysis results with 42.4 months of median follow-up demonstrated marked improvements across all efficacy endpoints. Median overall survival reached 15.8 months in the serplulimab arm compared to 11.1 months in the placebo arm, representing a 40% reduction in death risk (stratified HR 0.60, 95% CI 0.49–0.73). The four-year overall survival rate was 21.9% (95% CI 17.6–26.6) versus 7.2% (95% CI 3.8–12.1) for serplulimab and placebo groups, respectively.
Progression-free survival according to independent radiology review committee assessment showed median values of 5.8 months versus 4.3 months (stratified HR 0.47, 95% CI 0.38–0.57). Subgroup analyses revealed consistent survival improvements across patient demographics, including age, sex, race, ECOG performance status, smoking history, brain metastasis status, and PD-L1 expression levels.
Safety profiles remained manageable, with serplulimab-related treatment-emergent adverse events of grade 3 or higher occurring in 136 patients (35.0%) compared to 57 patients (29.1%) in the placebo arm. No new safety signals emerged during the extended follow-up period.
Combination Strategies Show Promise in Squamous NSCLC
A phase 2 study led by Professor Yi-Long Wu from Guangdong Provincial People's Hospital evaluated HLX07 plus serplulimab with chemotherapy as first-line therapy for advanced squamous non-small cell lung cancer. Twenty-seven patients were enrolled and randomized to receive either 800 mg or 1000 mg of HLX07 combined with 300 mg serplulimab and chemotherapy.
With a median follow-up of 16.0 months, the independent radiology review committee-assessed confirmed objective response rate reached 69.2% (95% CI 38.6–90.9) in the 800 mg group and 71.4% (95% CI 41.9–91.6) in the 1000 mg group. Disease control rates were 92.3% and 100%, respectively. Median progression-free survival was 15.1 months in the lower dose group, while the higher dose group had not reached median PFS at data cutoff.
Gastrointestinal Cancer Applications Expand Treatment Options
Serplulimab demonstrated remarkable efficacy in HER2-positive gastric cancer when combined with trastuzumab and intensive chemotherapy. A phase 2 trial enrolled 40 patients with unresectable locally advanced or metastatic HER2-positive gastric cancer between July 2022 and September 2024. Among 37 evaluable patients, the objective response rate reached 92% (95% CI 0.87–0.96), with median progression-free survival not yet reached at 7.9 months median follow-up.
The safety profile proved manageable, with 38 patients (95%) experiencing adverse events of any grade. Grade 3 or higher adverse events occurred in 14 patients (35%), including two patients with grade 4 events. The most common adverse events included anemia (35%), neutropenia (23%), nausea and vomiting (20%), and leukopenia (20%).
For patients with gastric or gastroesophageal junction adenocarcinoma who failed first-line immunochemotherapy, the STILL trial demonstrated promising second-line activity. Forty-seven patients received serplulimab combined with lenvatinib and paclitaxel, achieving an objective response rate of 51.2% (95% CI 35.1–67.1%) among 41 evaluable patients. Median progression-free survival was 7.1 months, with median overall survival reaching 13.7 months.
Real-World Evidence Validates Clinical Trial Results
Multiple real-world studies confirmed serplulimab's effectiveness across diverse patient populations. In metastatic or locally advanced esophageal carcinoma, 104 patients treated with first-line serplulimab achieved an objective response rate of 40.0% (95% CI 29.8–50.9) and disease control rate of 97.8% (95% CI 92.2–99.7). Median real-world progression-free survival reached 12.0 months, with estimated 12-month survival rate of 73.5%.
A nationwide real-world study of serplulimab-based neoadjuvant therapy in esophageal cancer included 95 patients who underwent radical surgery. The pathological complete response rate was 23.16%, with major pathological response rate of 41.05%. R0 resection was achieved in 89 patients (93.68%), with tumor and nodal downstaging rates of 56.84% and 61.05%, respectively.
Pancreatic Cancer Combinations Show Exceptional Activity
Serplulimab demonstrated remarkable efficacy in metastatic pancreatic cancer when combined with gemcitabine, nab-paclitaxel, and stereotactic body radiotherapy. Forty-seven patients enrolled in a phase 2 trial achieved a 6-month progression-free survival rate of 78.48%, meeting the preset primary endpoint. The objective response rate reached 74.47%, including one complete response and 34 partial responses, with 100% disease control rate.
Median progression-free survival was 8.6 months, while median overall survival reached 15.5 months. The most frequent grade 3 drug-related adverse events included neutropenia (42.55%), leukopenia (40.43%), anorexia (38.30%), and fatigue (23.40%).
Dosing Flexibility Confirmed in Phase 1 Study
A phase 1 dose-finding study evaluated fixed-dose regimens of serplulimab in 37 patients with advanced solid tumors. Patients received 200 mg every 2 weeks, 300 mg every 3 weeks, 400 mg every 4 weeks, or 600 mg every 6 weeks. No dose-limiting toxicity was reported across any regimen, and maximum tolerated dose was not determined.
Treatment-related adverse events occurred in 19 patients (51.4%), with 7 patients (18.9%) experiencing grade 3 or higher events. Six patients achieved partial response, resulting in an overall response rate of 17.1%. Pharmacodynamic analyses revealed similar PD-1 receptor occupancy profiles across dose groups, suggesting dose-independent functional blockade.
The comprehensive ASCO 2025 data presentation reinforces serplulimab's position as a versatile immunotherapy option across multiple cancer types, with ongoing phase 3 trials expected to further expand its therapeutic applications in combination with chemotherapy, targeted agents, and radiotherapy.
