Serplulimab Signals Potential Perioperative Paradigm Shift in Gastric Cancer

The phase 3 ASTRUM-006 trial evaluating the anti–PD-1 monoclonal antibody serplulimab (Hansizhuang) as neoadjuvant/adjuvant monotherapy treatment of gastric cancer has met its primary end point of event-free survival (EFS), according to an interim analysis.¹

In addition to showing a significant improvement in EFS, serplulimab in combination with chemotherapy elicited a pathologic complete response (pCR) rate that was more than threefold higher than the rate achieved with a placebo plus chemotherapy. As of data shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, median disease-free survival and overall survival (OS) were not reached.²

Along with the positive efficacy findings, the agent demonstrated a favorable safety profile, with no new safety signals reported. The most common any-grade treatment-related adverse events reported at the 2025 ASCO Annual Meeting were nausea, thrombocytopenia, fatigue, and thyroid dysfunction.²

While perioperative therapy combined with surgery is the standard of care for locally advanced gastric cancer, long-term survival remains suboptimal.² These data chart a potential new treatment pathway in the perioperative setting from adjuvant chemotherapy to a mono-immunotherapy regimen that could improve quality of life for patients.

“Surgery is the cornerstone of gastric cancer treatment, and perioperative therapy is critical to long-term survival. This study is the first to confirm the feasibility of replacing adjuvant chemotherapy with mono-immunotherapy in the postoperative setting. It not only opens a new path to consolidate surgical outcomes and reduce recurrence risk but also paves the way for innovation in clinical practice,” said Jiafu Ji, professor at Beijing Cancer Hospital and principal investigator of the study, in a press release.¹

What Is the Development Journey of Serplulimab?

The development journey of serplulimab, a PD-1 inhibitor, has been marked by positive efficacy and safety data and regulatory approvals in several lung cancer indications. To date, it is approved in squamous non–small cell lung cancer (sqNSCLC) and nonsquamous NSCLC in China,³ as well as in extensive-stage small cell lung cancer (ES-SCLC) in China, Southeast Asia, and in the European Union.⁴ The ASTRUM-006 results are the first to demonstrate its efficacy in gastric cancer.

The trial in question, ASTRUM-006, is a randomized, double-blind, multicenter study evaluating the safety and efficacy of serplulimab plus chemotherapy against placebo plus chemotherapy in patients with early-stage gastric cancer. The study enrolled 25 patients with resectable gastric/gastroesophageal junction adenocarcinoma who underwent neoadjuvant therapy and subsequently underwent surgery. The neoadjuvant therapeutic regimen consisted of 300 mg of serplulimab plus oxaliplatin chemotherapy for 3 weeks, lasting 3 cycles.

Serplulimab plus chemotherapy was also evaluated in the randomized, double-blind, phase 3 ASTRUM-005 trial (NCT04063163) involving 585 patients with ES-SCLC, the findings of which revealed significantly enhanced OS compared with placebo-chemotherapy (median OS, 15.4 months vs 10.9 months, respectively), equating to a hazard ratio of 0.63 (95% CI, 0.49–0.82; P <.001).⁵ Results from this trial ultimately supported the European Medicines Agency’s authorization of serplulimab (Hetronifly) for use in the European Union in February 2025.⁴

Furthermore, the phase 3 ASTRUM-004 trial (NCT04033354) investigated serplulimab plus chemotherapy compared to placebo-chemotherapy in patients with advanced sqNSCLC.⁶ Here, the primary end point of progression-free survival was met at the first interim analysis (HR, 0.53; 95% CI, 0.42–0.67); in the final analysis, there was significantly improved median OS in the compared with the control arm (HR, 0.73; 95% CI, 0.58–0.93; P =.010). Data from this trial supported serplulimab’s approval in this indication by China’s National Medical Product Administration in December 2024.³

What Are the Next Steps in Clinical Development?

Based on the positive efficacy and safety findings from ASTRUM-006, the Independent Data Monitoring Committee (IDMC) that conducted the interim analysis has recommended early submission of a new drug application for serplulimab.

The sponsor, Shanghai Henlius Biotech, concurrently intends to continue investigating serplulimab-based combinations in a global phase 3 study involving patients with metastatic colorectal cancer.

REFERENCES:

1. Phase 3 clinical trial of HANSIZHUANG plus chemotherapy meets primary endpoint in neoadjuvant/adjuvant gastric cancer, greenlighting early NDA submission. News release. Shanghai Henlius Biotech. October 9, 2025. Accessed October 15, 2025. https://tinyurl.com/5bdfrk38

2. Zhan H, Liu L, Sun W, et al. Neoadjuvant serplulimab in combination with chemotherapy for locally advanced gastric or gastro-esophageal junction cancer. J Clin Oncol. 2025;43(suppl 16):4030. doi:10.1200/JCO.2025.43.16_suppl.4030

3. Henlius’ Novel Anti-PD-1 mAb HANSIZHUANG (Serplulimab) Receives NMPA Approval for the Treatment of nsNSCLC. News release. Shanghai Henlius Biotech. December 3, 2024. Accessed October 16, 2025. https://tinyurl.com/4j227vuf

4. Serplulimab Approved in the EU for First-Line Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC). News release. Shanghai Henlius Biotech. February 5, 2025. https://tinyurl.com/mr3au96b

5. Cheng Y, Han L, Wu L, et al. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer. JAMA. 2022;328(12):1223-1223. doi:10.1001/jama.2022.16464

6. Zhou C, Hu Y, Ekaterine Arkania, et al. A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004). Cancer Cell. 2024;42(2):198-208.e3. doi:10.1016/j.ccell.2023.12.004