On March 26, the antibody coupling drug (ADC) Enhertu (fam-trastuzumab deruxtecan-nxki, DS-8201) jointly developed by Daiichi Sankyo and AstraZeneca, targeting HER2, was In a phase 1 clinical trial of patients with previously treated HER2 overexpressing cancer, 55.6% of patients with non-small cell lung cancer (NSCLC) had their tumors reduced. In addition, Japan's Ministry of Health, Labour and Welfare (MHLW) announced on the 26th that it approved Enhertu for the treatment of patients with unresectable HER2-positive or metastatic breast cancer.
HER2 is a protein belonging to the human epidermal growth factor receptor family, which is overexpressed in a variety of cancers, including breast cancer, ovarian cancer, gastric cancer and lung cancer. HER2 mediates cell growth, differentiation and survival, and can promote the aggressive spread of cancer cells. Compared with HER2-negative cancers, HER2-positive tumors are more aggressive and are associated with shorter survival times, poorer overall survival rates, higher risk of recurrence, and central nervous system diseases.
Enhertu used the unique ADC technology of Daiichi Sankyo to link the human HER2 antibody trastuzumab to a new topoisomerase 1 inhibitor via a tetrapeptide linker, targeting cancer cells and delivering drugs to the cells internal. Compared with the usual chemotherapy, these new drugs can reduce the side effects of chemotherapy drugs. It is currently studying a variety of cancers used to treat HER2 expression, including breast cancer, gastric cancer, NSCLC, colorectal cancer (CRC), and patients with low HER2 expression. Last year, Enhertu was approved by the US FDA to treat HER2-positive, locally advanced or metastatic breast cancer patients who had previously received HER2 targeted therapies such as trastuzumab and pertuzumab.
A total of 60 cancer patients treated with HER2 overexpression or mutation participated in this phase 1 clinical study, including 18 patients with NSCLC, 20 patients with CRC, and several other patients with different tumor types. Data from the trial showed that Enhertu's treatment reduced tumors in 28.3% of patients and brought the patient's median progression-free survival (PFS) to 7.2 months. Among them, NSCLC patients had the highest objective response rate, of which 55.6% of patients had tumor shrinkage, and the median response time reached 10.7 months. The efficacy was more pronounced in NSCLC patients with HER2 mutations, and Enhertu's treatment relieved 72.7% of patients in this group. The median PFS of all NSCLC patients reached 11.3 months.
In addition, another study published in Cancer Discovery found that Enhertu's treatment achieved partial remission in NSCLC patients whose disease still progressed after another ADC (Kadcyla) treatment, reducing the patient's tumor by 70%.
"We are very satisfied with the results of this preliminary study," said Bob Li, MD, an oncologist at the Memorial Sloan Kettering Cancer Center: "Enhertu demonstrated changes in HER2 overexpression or HER2 mutations Early hope for the treatment standard for cancer patients, we look forward to continuing to advance this important research in future clinical trials. "