Shanghai Henlius Biotech announced that its anti-PD-1 monoclonal antibody HANSIZHUANG (serplulimab) in combination with chemotherapy has met the primary endpoint of event-free survival (EFS) in the phase 3 ASTRUM-006 trial for perioperative gastric cancer treatment. The breakthrough represents the world's first regimen to replace adjuvant chemotherapy with mono-immunotherapy in the perioperative setting, enabling an early New Drug Application (NDA) submission.
Trial Results Demonstrate Superior Efficacy
The ASTRUM-006 study, a randomized, double-blind, multi-centre phase 3 clinical trial, compared HANSIZHUANG or placebo in combination with chemotherapy as neoadjuvant/adjuvant monotherapy treatment for patients with early-stage gastric cancer. According to the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), the trial met its predefined efficacy criteria.
Compared with placebo plus chemotherapy, HANSIZHUANG plus chemotherapy significantly prolonged EFS and achieved a more than threefold higher pathological complete response (pCR) rate, with a significant reduction in the risk of recurrence. The combination regimen demonstrated a favorable safety profile, with no new safety signals identified.
Professor Jiafu Ji from Beijing Cancer Hospital, a leading principal investigator of the ASTRUM-006 study, commented: "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."
Addressing Significant Unmet Medical Need
Gastric cancer represents a major global public health challenge. According to the latest GLOBOCAN statistics, there were approximately 969,000 new cases and 660,000 deaths worldwide in 2022, ranking it fifth in both incidence and mortality among all cancers. While radical surgery remains the primary treatment modality, optimizing perioperative strategies has become pivotal to improving long-term patient survival.
The field faces a dual challenge in current clinical practice. No immunotherapy has yet been formally approved for this specific indication, and only a limited number of phase 3 studies have successfully met their primary endpoints. Additionally, factors such as slow postoperative recovery and poor chemotherapy tolerance often prevent patients from completing adjuvant chemotherapy, thereby compromising their long-term survival outcomes.
Professor Lin Shen from Beijing Cancer Hospital, a leading principal investigator of the ASTRUM-006 study, stated: "The positive results from this study confirm the significant potential of serplulimab in the perioperative setting for gastric cancer. The innovative exploration of a 'chemotherapy-free, mono-immunotherapy' regimen during the adjuvant phase tangibly improves patients' quality of life, offering a new approach for optimizing clinical strategies."
Differentiated Mechanism of Action
HANSIZHUANG demonstrates unique advantages in treating various solid tumors via its differentiated mechanism. The drug not only induces stronger PD-1 internalization—reducing PD-1 receptor presence on T cells for rapid and potent immune activation—but also minimizes PD-1-mediated recruitment of the co-stimulatory molecule CD28, thereby preserving CD28 signaling, enhancing downstream AKT activity, and promoting sustained T-cell activation.
The ASTRUM-006 study innovatively employed a "chemotherapy-free" serplulimab monotherapy strategy in the adjuvant setting. This approach maintained therapeutic efficacy while effectively circumventing toxicity related to conventional chemotherapy, significantly improved patients' quality of life, and provided a new clinical option. The success of this trial marks a pivotal shift in perioperative gastric cancer care—from a conventional intensity-driven paradigm toward a more refined "high-efficacy, low-toxicity" treatment model.
Expanding GI Cancer Portfolio
Gastrointestinal cancer is a strategically core therapeutic area for Henlius, with dedicated focus and extensive development. The company has built a diversified product portfolio spanning from immunotherapy to targeted agents, addressing high-incidence GI cancers such as esophageal, gastric, and colorectal cancers.
In esophageal cancer, HANSIZHUANG received approval in China in September 2023 for the first-line treatment of esophageal squamous cell carcinoma (ESCC). Beyond the positive outcomes achieved with HANSIZHUANG in the neoadjuvant/adjuvant setting, the company's internally developed HER2 mAb, HLX22, is challenging the current first-line standard of care for HER2-positive advanced gastric cancer through an international multi-centre, head-to-head phase 3 trial.
Dr. Jason Zhu, Executive Director and Chief Executive Officer of Henlius, said: "Gastrointestinal cancer is a core therapeutic area of dedicated focus for Henlius. The successful achievement of the primary endpoint in the phase 3 perioperative study of HANSIZHUANG in gastric cancer marks a pivotal breakthrough for the company. We are committed to actively advancing the translation of these findings into clinical practice, with the goal of bringing benefits to patients at the earliest opportunity."
