Shanghai, China, January 26, 2025 – Shanghai Henlius Biotech, Inc. (2696. HK) announced that the latest clinical data of two Henlius novel products, the anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab) and an innovative anti-HER2 mAb HLX22, were presented in poster sessions at the 2025 ASCO Gastrointestinal Cancers Symposium (ASCO GI).

HANSIZHUANG (serplulimab) is a recombinant humanised anti-PD-1 monoclonal antibody（mAb）injection independently developed by Henlius, and the world's first anti-PD-1 mAb approved for the first-line treatment of SCLC. Up to date, it has been approved in China and several Southeast Asian countries. 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. In China, it has been approved by the NMPA for the treatment including squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC), benefiting over 90,000 patients. Moreover, a wide variety of clinical trials on immuno-oncology combination therapies in differentiated indications has been initiated by the company to further explore the efficacy of HANSIZHUANG for the treatment of patients with metastatic colorectal cancer (mCRC), gastric cancer (GC), and limited-stage small cell lung cancer (LS-SCLC),etc.

HLX22 is an innovative anti-HER2 mAb introduced from AbClon, Inc. and further investigated and developed by Henlius. Pre-clinical studies showed that the co-treatment with HLX22 and trastuzumab synergistically inhibited tumour cell proliferation and apoptosis, which led to enhanced anti-tumour activity in vitro and in vivo. HLX22-GC-201, the phase 2 clinical trial of HLX22 combined with trastuzumab showed that adding HLX22 to HLX02 (trastuzumab for injection) + XELOX improved survival and anti-tumour response in patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer in the first-line setting, with a manageable safety profile^[1,2]. Up to date, the phase 3 international multicenter clinical study of HLX22 in combination of trastuzumab and chemotherapy for the treatment of HER2 positive advanced G/GEJ cancer has received regulatory approvals in China, the U.S., Japan and Australia, respectively. And the first subject has been dosed for this MRCT in China.

The latest data of the studies released at ASCO GI 2025 are as follows:

HLX10

Title

Updated efficacy and subgroup analysis of first-line serplulimab plus bevacizumab and XELOX versus placebo plus bevacizumab and XELOX in metastatic colorectal cancer: a phase 2/3 study

Study design

A total of 114 patients with mCRC and no prior systemic therapy were randomized 1:1 (serplulimab arm, n = 57; placebo arm, n = 57) to receive intravenous (IV) serplulimab (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (group A) or placebo plus bevacizumab and XELOX (group B) once every 3 weeks. Stratification factors were PD-L1 expression level, ECOG PS score, and primary tumor site. The primary endpoint was independent radiological review committee (IRRC)-assessed PFS per RECIST 1.1. Secondary endpoints included other efficacy endpoints, safety, pharmacokinetics, biomarker explorations, and quality-of-life assessments.

Results

In the phase 2 part, by the data cutoff of June 30, 2024, sustained improvements in PFS (16.6 vs. 10.7 months, stratified HR 0.66, 95% CI 0.37–1.19) and DOR (17.7 vs. 11.3 months, stratified HR 0.45, 95% CI 0.20–0.98) were observed for patients in group A compared to group B in the modified intent-to-treat population (n = 112; two patients in group A did not receive any intended study treatment). A trend of PFS and OS benefits was similarly observed for the patients with a microsatellite stable (MSS) status (PFS: 16.8 vs. 10.1 months, stratified HR 0.65, 95% CI 0.33–1.29; OS: 23.5 vs. 20.2 months, stratified HR 0.79, 95% CI 0.45–1.38). Most irAEs were mild (grade 1–2); grade ≥3 irAEs occurred in 12.7% of the patients in group A, and 1.8% of the patients in group B.

Conclusion

With a median follow-up duration of 31.0 months, improved survival benefits demonstrated with the addition of serplulimab were maintained in the first-line treatment of mCRC patients including those with MSS status alongside a manageable safety profile. Serplulimab plus bevacizumab and XELOX has promising potential to be an alternative first-line option in mCRC. The phase 3 part of this study conducted in patients with MSS mCRC is currently ongoing (NCT04547166).

Title

Safety and Efficacy of Perioperative Chemotherapy Combined with PD-1 Inhibitor versus Chemotherapy with D2 plus Gastrectomy and PAND in Gastric Cancer with PAN Metastasis: A Single-Center Retrospective Cohort Study

Study design

We retrospectively reviewed medical records of gastric cancer patients with isolated No. 16a2/b1 PAN metastasis treated at Zhejiang Cancer Hospital, Hangzhou, China, between January 2011 and February 2024. The analysis included 133 patients; those who received immunochemotherapy were assigned to Group A (n=62), and those who received chemotherapy alone were assigned to Group B (n=71). The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included safety, major pathological response (MPR), R0 resection, and survival.

Results

In the entire cohort, 95 patients (71.4%) were male, with a median age of 66 years. All patients in Group A received anti-PD-1 monoclonal antibodies as immunotherapy, with 32 patients treated with serplulimab and 30 patients treated with tislelizumab. A total of 26 patients (19.5%) achieved pCR. The pCR and MPR rates were significantly higher in Group A (Table 2). The 2-year OS rates for Group A and Group B were 90.3% and 62.9% (P=0.011). Subgroup analysis of Group A showed patients with PD-L1 CPS ≥5 have a better pCR and MPR CPS <5. A total of 122 patients (91.7%) experienced any grade of adverse events (AEs) during perioperative treatment, 56 (90.3%) in Group A and 66 (92.9%) in Group B. All AEs were well-controlled, and no treatment-related deaths were reported.

Conclusion

The addition of a PD-1 inhibitor to chemotherapy significantly improves the pathological response rate and prognosis in gastric cancer patients with PAN. Notably, the combination did not increase adverse events.

HLX22

Title

HLX22 plus trastuzumab and XELOX for first-line treatment of HER2-positive locally advanced or metastatic gastric/gastroesophageal junction cancer (G/GEJC): Updated results with additional patients

Study design

Patients with locally advanced or metastatic HER2-positive G/GEJC and no prior systemic antitumor therapy were enrolled. Herein reported are results from Stage 2 of the study. Eligible patients were randomized to receive either HLX22 + trastuzumab + XELOX or placebo + trastuzumab + XELOX in 3-week cycles. Primary endpoints were independent radiology review committee (IRRC)-assessed progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included other efficacy and safety endpoints.

Results

As of June 30, 2024, 62 patients were randomized to the respective groups (31 vs 31), of whom 51 (82.3%) patients were male. Median follow-up duration was 20.3 and 24.0 months for the respective groups. The efficacy results are shown in Table 1. Treatment-emergent adverse events (TEAEs) were reported in 30 (96.8%) and 31 (100%) patients, and HLX22- or placebo-related TEAEs of grade 3 or higher were reported in 9 (29.0%) and 6 (19.4%) patients in the respective groups. One patient (3.2%) in the placebo + trastuzumab + XELOX group had a grade 5 HLX22-/placebo-related TEAE. 

Conclusion

With a manageable safety profile, the addition of HLX22 to first-line treatment with trastuzumab plus XELOX conferred survival benefit for HER2-positive G/GEJC patients.