On the 27th, AbClon announced the first patient dosing in Japan for the international multicenter Phase 3 clinical trial (HLX22-GC-301) of AC101 in combination with trastuzumab and chemotherapy. AC101, which was licensed out by AbClon to Henlius, is being developed under the code name HLX22 as a first-line treatment for HER2-positive advanced gastric cancer and gastroesophageal junction (G∙GEJ) cancer.

The principal investigator of the clinical trial is Professor Lin Shen from Peking University Cancer Hospital. In China the first patient dosing of HLX22 has already carried out and the global Phase 3 trial is also underway in the United States. Particularly in Japan, patient dosing proceeded rapidly after a recent investigator meeting, which the company demonstrated high interest and active commitment to the clinical trial. To date, no dual HER2 blockade therapy like this has been commercially approved worldwide for HER2-positive gastric cancer.

Gastric and gastroesophageal junction cancer still remain as a global health problem. In 2022, approximately 1 million new cases occurred worldwide, and in Japan, gastric cancer ranked the third in incidence and mortality among all cancers. In the same year, about 127,000 new cases were reported in Japan, with 44,000 deaths.

Gastric and gastroesophageal junction cancers are often diagnosed at an advanced stage, leading to poor prognosis, with a 5-year relative survival rate of only 6%. Among gastric cancer patients, about 12-23% are HER2-positive, which is known to have a worse prognosis than HER2-negative cases. The current standard first-line treatment for HER2-positive locally advanced or metastatic cancer is a combination of trastuzumab and chemotherapy, with immunotherapy additionally recommended based on PD-L1 expression (CPS (Combined Positive Score) >1). However, there are still limitations in improving treatment effectiveness and prognosis.

HLX22 is an innovative anti-HER2 monoclonal antibody developed by AbClon, which binds to a different site from trastuzumab (HER2 extracellular domain IV) and simultaneously inhibits HER2 homodimers and HER2∙EGFR heterodimers. This mechanism facilitates HER2 receptor internalization and dimer breakdown, maximizing anticancer effects. In Phase 2, HLX22 was administered in combination with HLX02 (trastuzumab biosimilar) and XELOX (chemotherapy) as a first-line treatment for HER2-positive locally advanced/metastatic gastric cancer, resulting in improved treatment efficacy and manageable safety. These study results were officially presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) this year.

The Phase 3 trial is a double-blind, randomized, controlled, multicenter study. It aims to compare the efficacy and safety of the HLX22+trastuzumab+chemotherapy combination group versus the trastuzumab+chemotherapy (±pembrolizumab) control group in patients with HER2-positive locally advanced or metastatic gastric and gastroesophageal junction cancers.

Participants are randomly assigned in a 1:1 ratio to either the experimental group (HLX22 15mg/kg intravenous infusion + trastuzumab + chemotherapy) or the control group (placebo + trastuzumab + chemotherapy ± pembrolizumab). The primary endpoints are progression-free survival (PFS) and overall survival (OS) assessed by the Independent Radiological Review Committee (IRRC) according to RECIST 1.1 (latest version), and secondary endpoints include investigator-assessed PFS, objective response rate (ORR), duration of response (DOR), quality of life, safety, immunogenicity, and pharmacokinetic characteristics.

The company stated, "With the rapid progress of this clinical trial, Henlius' stock price has also been rising recently, reflecting expectations for HLX22's clinical trial results. Industrial interest is growing as to whether it can establish itself as a new treatment option that complements the limitations of existing HER2 therapies."

They added, "Depending on the results of this Phase 3 trial, its potential for future commercialization is also drawing attention."

Furthermore, they emphasized, "HLX22's innovative approach, which precisely blocks cancer cell growth signals, has the potential to change the paradigm of cancer treatment. In particular, it can offer hope to cancer patients who have difficulty seeing results with existing treatments."