Shanghai, China, May 9, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the latest results on Henlius’ self-developed innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab, trade name: Hetronifly® in Europe) were presented at the congress. Among them, a phase 2 study evaluating serplulimab combined with concurrent chemoradiotherapy as neoadjuvant treatment for resectable esophagogastric junction adenocarcinoma will be orally presented at the 16th International Gastric Cancer Congress (IGCC 2025). Among them, a phase 2 study evaluating serplulimab combined with concurrent chemoradiotherapy as neoadjuvant treatment for resectable esophagogastric junction adenocarcinoma was orally presented.
According to GLOBOCAN data, in 2022 there were around 1 million new cases of gastric/gastroesophageal junction (G/GEJ) cancer worldwide, posing a major challenge to global public health. In China, the incidence and mortality of G/GEJ rank fifth and third among all malignant tumors, respectively, with over 358,600 new cases and 260,300 deaths in 2022 [1].
HANSIZHUANG (serplulimab), Henlius’ first self-developed innovative anti-PD-1 mAb, is the world’s first anti-PD-1 mAb for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Up to date, it has been approved in over 30 countries and regions, including China, Europe and Southeast Asia, benefiting over 100,000 patients. Underpinned by the patient-centric strategy, Henlius has carried out a differentiated and multi-dimensional layout in the field of gastrointestinal cancer and lung cancer, covering a wide variety of indications. Up to date, it has been approved for the treatment of squamous non-small cell lung cancer (sqNSCLC), ES-SCLC, esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC). 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 company is actively advancing a phase 3 clinical trial of HANSIZHUANG plus chemotherapy as neoadjuvant/adjuvant therapy for gastric cancer, as well as the international multi-centre phase 3 clinical trial (ASTRUM-015) of serplulimab in combination with bevacizumab and chemotherapy in first-line treatment of metastatic colorectal cancer (mCRC).
The latest data of the studies released at IGCC 2025 are as follows:
Oral presentation
Title
Neoadjuvant Serplulimab with Concurrent Chemoradiotherapy in Resectable Esophagogastric Junction Adenocarcinoma: Phase 2 Updated Results
Study design
Eligible patients with resectable EGJ（cT3-4 or N+M0）adenocarcinoma received neoadjuvant Serplulimab (300 mg) plus SOX (oxaliplatin 130 mg/㎡; TS1 40-60 mg) for the first cycle, followed by Serplulimab with concurrent chemoradiotherapy (oxaliplatin 100 mg/㎡, TS1 40-60 mg; radiotherapy dose 45 Gy/ 25 fractions) during the second and third cycles. Surgery was performed 6-8 weeks after chemoradiotherapy.
Results
From March 2023 to November 2024, 24 patients were enrolled and 19 patients underwent radical resection. The R0 rate was 100%. pCR rate was 26.3%, MPR rate was 36.8%. T downstaging rate 78.9%, ypN0 89.5%. The median DFS was not reached. Microsatellite stable status was 100%. PD-L1 CPS expression: <1 (5.3%), 1-5 (42%), >5 (52.6%), >10 (31.6%). PD-L1 expression was associated with pathological response, with MPR rates of 57.1% for CPS >5 and 14.3% for CPS ≤5. Minimal residual disease positivity (MDR+) before enrollment was 68.7%, and 6 MRD+ patients converted to MRD- after neoadjuvant therapy. Grade ≥3 adverse events occurred in 33.3% of patients, with manageable treatment-related adverse events.
Conclusion
Neoadjuvant Serplulimab with concurrent chemoradiotherapy showed promising efficacy for locally advanced resectable EGJ adenocarcinoma. Improved R0 and ypN0 rate may change the surgical procedure in the future. Follow-up will assess correlations between biomarkers and outcomes.
Poster Presentation
Title
Efficacy and Safety of Neoadjuvant Anti-PD-1, Thymosin, and SOX in cStage III Gastric Cancer
Study design
Between June and November 2024, all 30 participants were enrolled. Patients received three cycles of serplulimab (300 mg IV, Q3W), thymosin α-1 (4.8 mg SC, biweekly), and the SOX regimen, followed by radical gastrectomy with D2 lymphadenectomy 2–6 weeks post-treatment. Key outcomes included pathological responses (pCR/MPR) and treatment-related adverse events (TRAEs).
Results
Median age was 66 years (37–75), 90% were male, and 46.7% had gastroesophageal junction tumors. The median PD-L1 CPS was 3 (0–30), and 93.3% were pMMR/MSS. Patients were categorized as group A (under treatment, n=12), B (completed neoadjuvant phase, awaiting surgery, n=7), and C (post-surgery, n=11). TRAEs occurred in 66.7% patients, with diarrhea being most common (46.7%), and no grade 5 events reported. Among groups B+C (n=18), the ORR was 83.3%, and the disease control rate reached 94.4%. In group C cases (n=11), 100% achieved R0 resection, pathological responses included 18.2% pCR (TRG=0) and 45.5% MPR. Higher CD3+ CD4+ T cell counts correlated with pCR/MPR (P=0.041/0.029), outperforming PD-L1 and MSI as predictors.
Conclusion
Combination of anti-PD-1, thymosin α-1, and SOX demonstrated promising efficacy and manageable toxicity in neoadjuvant setting for locally advanced gastric cancer, independent of CPS selection. Further follow-up is ongoing to confirm long-term clinical benefits.
【Reference】
[1] Bray F, Laversanne M, Sung H, et al. CA Cancer J Clin. 2024: 1-35.
