Shanghai Henlius Biotech presented promising clinical data for two of its novel products, HLX22 and serplulimab (HANSIZHUANG), at the 2024 ASCO Gastrointestinal Cancers Symposium. These studies highlight the potential of these therapies in improving outcomes for patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer and metastatic colorectal cancer (mCRC).
HLX22 in HER2-Positive Gastric/Gastroesophageal Junction Cancer
Gastric/gastroesophageal junction (G/GEJ) cancer poses a significant global health challenge, with over 1 million new cases estimated in 2020. The prognosis for advanced G/GEJ cancer is poor, with a 5-year survival rate of only 6%. For HER2-positive patients, outcomes have historically been even worse. The phase 2 study (HLX22-GC-201) investigated HLX22, an innovative anti-HER2 mAb, in combination with trastuzumab (HLX02) and XELOX chemotherapy as a first-line treatment for HER2-positive locally advanced or metastatic G/GEJ cancer. HLX22 binds to HER2 subdomain IV, a different site than trastuzumab, allowing for simultaneous binding and enhanced antitumor activity.
The study randomized patients to receive HLX22 (25 mg/kg or 15 mg/kg) plus HLX02 and XELOX, or placebo plus HLX02 and XELOX. Results indicated that adding HLX22 to HLX02 + XELOX improved survival and antitumor response. As of the data cutoff on July 30, 2023, the median follow-up was 14.3 months. Treatment-related adverse events (TRAEs) occurred in most patients across all groups, with serious TRAEs observed in 27.8%, 5.9%, and 5.6% of patients in the respective groups. One patient in the placebo group experienced a grade 5 TRAE.
Serplulimab in Metastatic Colorectal Cancer
Colorectal cancer (CRC) is a prevalent malignancy worldwide, with over 1.9 million new cases and 900,000 deaths estimated in 2020. The standard of care for metastatic CRC (mCRC) typically involves a VEGF inhibitor, such as bevacizumab, combined with systemic chemotherapy. The phase 2/3 study (HLX10-015-CRC301) evaluated serplulimab, an anti-PD-1 monoclonal antibody, in combination with HLX04 (a bevacizumab biosimilar) and XELOX as a first-line treatment for mCRC.
The phase 2 portion of the study randomized patients to receive serplulimab (300 mg Q3W) plus HLX04 (7.5 mg/kg Q3W) and XELOX, or placebo plus bevacizumab and XELOX. The primary endpoint was investigator-reviewed RECIST 1.1-assessed PFS. Results demonstrated that serplulimab plus HLX04 and XELOX significantly prolonged PFS compared to placebo plus bevacizumab and XELOX (17.2 vs. 10.7 months; HR 0.60, 95% CI 0.31–1.14). Median OS was not reached in either group (HR 0.77, 95% CI 0.41–1.45). Grade ≥3 treatment-related adverse events (AEs) were reported in 65.5% and 56.1% of patients in the serplulimab and placebo groups, respectively. Treatment-related deaths occurred in 7.3% and 5.3% of patients in the respective groups.
The study concluded that serplulimab plus HLX04 and XELOX is a promising first-line treatment option for metastatic CRC patients and warrants further investigation.
