Recently, Hengrui Pharmaceuticals' subsidiaries, Shanghai Shengdi Pharmaceuticals Co., Ltd. and Suzhou Shengdia Biopharmaceuticals Co., Ltd. have received the Approval Notice of Drug Clinical Trial issued by the State Drug Administration, which authorizes to conduct the Phase Ib/II clinical study of Adebelizumab Injection in combination with SHR-A1811 and chemotherapy for HER2-expressing advanced adenocarcinoma of the stomach or the gastroesophageal junction.

In 2020, gastric cancer ranked 5th in global cancer incidence and 4th in mortality. Among them, 43.9% of new cases and 48.6% of deaths will occur in China, with 479,000 new cases and 374,000 deaths, both ranking third in China in terms of cancer incidence and mortality. Human Epidermal Growth Factor Receptor (HER2)-positive gastric cancer is a unique subtype of the disease, which requires different diagnostic and therapeutic strategies from HER2-negative gastric cancer. The global reported HER2-positive rate of gastric cancer is 7.3%-20.2%, and the HER2-positive rate of gastric cancer in China is 12-13%.

Although the existing treatments for HER2-expressing advanced gastric or gastroesophageal adenocarcinoma have achieved certain efficacy, the median OS of first-line treatment for HER2-positive advanced gastric cancer is only 16.0-20.0 months, and immunotherapy has not yet been approved in China, while that of first-line treatment for HER2-negative advanced gastric cancer (including HER2-poorly expressing) in combination with immunotherapy is still unsatisfactory. Therefore, exploring novel antibody-coupled drug combination therapies may provide more therapeutic options for a wide range of tumor patients.

Hengrui Pharmaceuticals has independently developed HER2-targeted antibody-drug coupling (ADC), which can induce apoptosis by binding to and endocytosing HER2-expressing tumor cells, releasing toxins through protease shearing in tumor cell lysosomes, and inducing cell-cycle blockade. SHR-A1811 is currently undergoing a number of phase I to phase III clinical studies, covering advanced solid tumors with HER2 expression or mutation, advanced gastric cancer or gastroesophageal adenocarcinoma, advanced colorectal cancer, advanced non-small cell lung cancer, metastatic breast cancer, and postoperative adjuvant treatment for early-stage breast cancer, etc. In February, 2024, SHR-A1811 for injection for the indication of HER2-positive advanced gastric cancer or gastroesophageal adenocarcinoma that had failed at least one line of prior anti-HER2 therapy was accepted by the Drug Review Center of the State Drug Administration (DRC) as a breakthrough treatment for the following indications State Drug Administration Drug Evaluation Center into the breakthrough therapeutic varieties.

Adebelizumab is a humanized anti-PD-L1 monoclonal antibody independently developed by Hengrui Pharmaceuticals, which can block the PD-1/PD-L1 pathway that leads to tumor immune tolerance by specifically binding to PD-L1 molecules, and reactivate the anti-tumor activity of the immune system, so as to achieve the purpose of tumor treatment. Adebelizumab injection (trade name: Ariel®) has been approved for marketing in 2023, and the approved indication is for the first-line treatment of patients with extensive-stage small cell lung cancer in combination with carboplatin and etoposide. The product has been included in the special drug reimbursement catalog of "Huiminbao" in Beijing, Shanghai, Chengdu and other places. A number of clinical studies of Adebelizumab Injection are underway to evaluate its anti-tumor effects in various solid tumors, including non-small cell lung cancer, small cell lung cancer, esophageal cancer, liver cancer, advanced gastric cancer or gastroesophageal adenocarcinoma.

Research on the synergistic mechanism of HER2 ADC in combination with immunotherapy has shown that HER2 receptor-targeted therapies have complex cross-talk mechanisms with immunotherapy. Combining the mechanisms of different drugs and data from similar drug studies, adalimumab injection in combination with SHR-A1811 and chemotherapy may provide new therapeutic options for patients with HER2-positive advanced gastric cancer and patients with gastric cancer with low expression of HER2. provide new therapeutic options.

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