HER2, the first ADC drug for HER2-positive gastric cancer, approved in Japan


Daiichi Sankyo recently announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved the HER2-targeted antibody conjugate (ADC) Enhertu (fam-trastuzumab deruxtecan, DS-8201) for the treatment of HER2-positive unresectable Patients with advanced or recurrent gastric cancer. Previously, MHLW already grants SAKIGAKE (Innovative Drug) qualification to Enhertu for the treatment of HER2-positive gastric cancer. The drug is developed globally by Daiichi Sankyo and AstraZeneca, and Daiichi Sankyo reserves Japanese rights.

Enhertu is the first ADC drug approved for the treatment of HER2-positive gastric cancer. It will bring meaningful therapeutic advancements to this type of cancer. This approval also marks Enhertu’s second indication approved by MHLW within 6 months. In March of this year, Enhertu was approved in Japan. For the treatment of HER2-positive, unresectable or metastatic breast cancer patients who have recurred after previous chemotherapy. Limited to patients who are ineffective or intolerant to standard treatments.

Once the disease progresses after the initial use of the anti-HER2 regimen, treatment options are very limited. Compared with chemotherapy in patients with HER2-positive metastatic gastric cancer who have previously received chemotherapy and anti-HER2 therapy. Enhertu is the first and only HER2-targeted therapy to show a significant prolongation of overall survival (OS). Based on the strong efficacy in clinical trials, Enhertu will become the new standard of care for the clinical treatment of such patients.

It should be pointed out that the efficacy and safety of Enhertu in HER2-positive unresectable or recurrent gastric cancer patients who have not previously received trastuzumab (trastuzumab, HER2 targeted therapy) regimen have not been determined.

This approval is based on the results of the open-label, randomized Phase 2 DESTINY-Gastric01 trial. The trial enrolled 187 patients HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) patients who had previously received 2 or more regimens (including 5- FU, platinum-containing chemotherapy, trastuzumab) but the disease progressed. In the study, patients were randomly assigned at a ratio of 2:1 and received Enhertu (6.4 mg/kg) or chemotherapy (paclitaxel or irinotecan monotherapy) selected by the research investigator, once every three weeks.

The results showed that the study reached the primary and key secondary endpoints. Compared with the chemotherapy group, the Enhertu treatment group achieved statistically and clinically significant improvements in objective response rate and overall survival.

The specific data are: Among 175 evaluable patients (including 140 Japanese patients), the independent central review (ICR) assessment: (1) The ORR of the Enhertu group was 51.3% (95%CI: 41.9-60.5%), chemotherapy The group was 14.3% (95%CI: 6.4-26.2%). In a pre-specified interim analysis, the risk of death was reduced by 41% than the chemotherapy group (HR=0.59; 95%CI: 0.39-0.88; p=0.0097). The median OS was 12.5 months in the Enhertu group and 8.4 months in the chemotherapy group.

In this trial, the safety and tolerability of Enhertu are consistent with previously reported Enhertu trials. Among 125 patients (including 99 Japanese patients) treated with Enhertu, 122 (97.6%) had drug-related adverse reactions. The most common adverse reactions were neutropenia (78 cases, 62.4%), nausea (72 cases, 57.6%), decreased appetite (66 cases, 52.8%), anemia (51 cases, 40.8%), thrombocytopenia ( 48 cases, 38.4%), leukopenia (47 cases, 37.6%), 43 cases of fatigue (34.4%), diarrhea (31 cases, 24.8%), alopecia (28 cases, 22.4%), decreased lymphocyte count (27 cases) , 21.6%), vomiting (26 cases, 20.8%) and others. Among Japanese patients, 11 out of 99 cases developed interstitial lung disease (ILD, 11.1%).