On October 9, HENLIUS announced that its self-developed PD-1 inhibitor H-drug (serplulimab) achieved the primary endpoint in its Phase III clinical trial for gastric cancer perioperative treatment (ASTRUM-006), becoming the world's first treatment regimen to replace postoperative adjuvant chemotherapy with immunotherapy monotherapy in gastric cancer perioperative setting.

This study innovatively adopted a "chemotherapy-free" H-drug monotherapy strategy in the adjuvant treatment phase, significantly improving event-free survival (EFS), with pathological complete response (pCR) rates more than three times higher than the control group, while significantly reducing recurrence risk. Against the backdrop of K-drug (pembrolizumab) and O-drug (nivolumab) consecutively failing in gastric cancer perioperative treatment, H-drug's success is particularly noteworthy, marking a critical leap in gastric cancer treatment from "simple intensive therapy" to "high-efficacy, low-toxicity" precision medicine approach.

**Breakthrough Design Leads Treatment Paradigm Shift, H-Drug Becomes New Solution for Recurrence and Chemotherapy Tolerance Issues**

Gastric cancer represents a major global public health challenge, with approximately 969,000 new cases and 660,000 deaths worldwide in 2022, ranking fifth in both incidence and mortality among all cancers. Currently, radical surgery remains the only curative treatment for gastric cancer. However, locally advanced gastric cancer has a postoperative recurrence rate of 40%-70%, with five-year survival rates after second surgery being less than 25%.

Current gastric cancer perioperative treatment relies on chemotherapy as the standard regimen, but recurrence rates remain high, with five-year overall survival rates still under 50%. In clinical practice, patients often struggle to complete adjuvant chemotherapy due to slow postoperative recovery or poor chemotherapy tolerance, affecting long-term survival benefits.

The innovative design of the ASTRUM-006 study was specifically created to address this clinical dilemma. ASTRUM-006 is a randomized, double-blind, multicenter Phase III clinical study targeting early-stage gastric cancer patients, designed to evaluate the clinical efficacy and safety of H-drug combined with chemotherapy versus placebo combined with chemotherapy in neoadjuvant/monotherapy adjuvant treatment for early-stage gastric cancer patients.

The most remarkable feature of this study is its innovative treatment strategy: using H-drug combined with chemotherapy in the neoadjuvant treatment phase, while switching to H-drug monotherapy in the adjuvant treatment phase, replacing traditional postoperative adjuvant chemotherapy.

According to interim analysis results from the independent data monitoring committee, the study met its preset superiority standards. Compared to placebo combined with chemotherapy, H-drug combined with chemotherapy significantly improved EFS, with pathological complete response rates more than three times higher than the control group, and patient recurrence risk significantly reduced. Meanwhile, the treatment regimen demonstrated good safety profile with no new safety signals identified.

H-drug's success is not coincidental, but stems from its differentiated molecular design mechanism. As HENLIUS's core anti-tumor drug, H-drug demonstrates significant advantages in treating various solid tumors through its unique mechanism of action.

The drug not only possesses stronger PD-1 endocytosis capability, reducing PD-1 receptors on T cell surfaces for rapid and potent immune activation, but also reduces PD-1 recruitment of co-stimulatory molecule CD28, thereby better preserving CD28 signal transduction, enhancing downstream AKT protein activity, and promoting sustained T cell activation. This differentiated mechanism enables H-drug to ensure efficacy while effectively avoiding traditional chemotherapy-related toxicity, greatly improving patient quality of life and providing entirely new options for clinical practice.

**Perioperative Market Potential Exceeds $6 Billion USD, World's First Chemotherapy-Free Regimen Shows Promise**

From a clinical value perspective, no immunotherapy has been approved globally for gastric cancer perioperative treatment. Previously, Merck's K-drug in the KEYNOTE-585 study, despite an average follow-up of 59.9 months, failed to achieve statistically significant improvement in event-free survival with its combination chemotherapy group.

Similarly, Bristol Myers Squibb's O-drug in the ATTRACTION-5 study also failed to demonstrate significant statistical differences. Against this backdrop, H-drug's success not only overcomes gastric cancer perioperative treatment challenges but, more importantly, establishes the scientific foundation for the world's first postoperative chemotherapy-free regimen for gastric cancer.

Professor Ji Jiafu from Peking University Cancer Hospital, principal investigator of the ASTRUM-006 study, noted: "Surgery is the core component of gastric cancer treatment, and perioperative treatment directly affects patients' long-term prognosis. This study is the first to confirm the feasibility of replacing adjuvant chemotherapy with immunotherapy monotherapy postoperatively, not only opening new pathways for consolidating surgical efficacy and reducing recurrence risk, but also bringing entirely new perspectives to clinical practice."

Professor Shen Lin from Peking University Cancer Hospital, another principal investigator, stated: "The positive results of this study confirm serplulimab's exceptional potential in gastric cancer perioperative treatment. Particularly in the adjuvant treatment phase, the innovative exploration of 'single immunotherapy without chemotherapy' regimen has substantially improved patient quality of life, providing new directions for optimizing clinical strategies."

From a market outlook perspective, this breakthrough signifies enormous market potential to be unleashed. According to Frost & Sullivan projections, the global gastric cancer drug market will grow from $22.1 billion in 2024 to $36.4 billion by 2030, with global gastric cancer perioperative market potential estimated to reach $6-7 billion.

H-drug, as the world's first PD-1 monoclonal antibody approved for first-line treatment of small cell lung cancer, has been approved in nearly 40 countries and regions, covering nearly half of the global population. Now, as the world's first to secure gastric cancer perioperative immunotherapy monotherapy treatment regimen, it will enjoy an extended market exclusivity period.