Enhertu Gains Approval in China as First HER2-Directed Therapy for HER2-Mutant Metastatic Non-Small Cell Lung Cancer

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has received conditional approval in China as a monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations and who have received a prior systemic therapy.

The conditional approval by the National Medical Products Administration (NMPA) was based on the positive results of the DESTINY-Lung02 and DESTINY-Lung05 Phase II trials. Full approval for this indication will depend on the clinical benefit of a confirmatory trial.

Each year in China, more than one million people are diagnosed with lung cancer, accounting for more than 40% of the world’s lung cancer patients – the majority are diagnosed with advanced disease. Approximately 2% to 4% of patients with NSCLC have tumours with activating HER2 mutations.

Ying Cheng, MD, PhD, Director of Jilin Lung Cancer Centre, China, and principal investigator of DESTINY-Lung05, said: “While there have been many advancements in the treatment of non-small cell lung cancer in China in recent years, patients with HER2-mutant disease have had few treatment options and none directed towards this specific type of lung cancer. This approval of Enhertu offers an important new targeted treatment for patients with this aggressive form of disease.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “This approval of Enhertu represents the first HER2-directed therapy approved in China for the treatment of HER2-mutant metastatic non-small cell lung cancer, marking an important step forward in how the disease can be treated. It also reinforces the importance of testing for predictive biomarkers in lung cancer at the time of diagnosis, including HER2 mutations, to ensure patients can receive the most appropriate treatment for their specific disease.”

Kiminori Nagao, Head of the Asia, South & Central America Business Unit, Daiichi Sankyo, said: “Since our initial approval of Enhertu for patients with HER2-positive metastatic breast cancer in China last year, we have remained committed to bringing this innovative antibody drug conjugate to more patients in China, especially those that have previously not been eligible for treatment with a HER2-directed therapy. Today’s milestone marks the fourth approval of Enhertu in China and follows the recent approval for HER2-positive metastatic gastric cancer, reinforcing its benefit across multiple HER2-targetable tumours.”

In DESTINY-Lung02, which included patients from Japan, Korea and Taiwan (China), patients with previously treated HER2-mutant metastatic NSCLC treated with Enhertu (5.4mg/kg) showed a confirmed objective response rate (ORR) of 49.0% (95% confidence interval [CI] 39.0-59.1), as assessed by blinded independent central review (BICR). Median duration of response (DoR) was 16.8 months (95% CI 6.4-non-evaluable [NE]). Median progression-free survival (PFS) was 9.9 months (95% CI 7.4-NE) and median overall survival (OS) was 19.5 months (95% CI 13.6-NE).

In DESTINY-Lung05, Enhertu (5.4mg/kg) demonstrated a consistent clinically meaningful response in patients in China with previously treated HER2-mutant metastatic NSCLC. Treatment with Enhertu resulted in a confirmed ORR of 58.3% (95% CI 46.1-69.8), as assessed by independent central review (ICR).

The safety profile of Enhertu in DESTINY-Lung02 and DESTINY-Lung05 were similar and generally consistent with previous clinical trials of Enhertu in lung cancer with no new safety concerns identified.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Enhertu is already approved for the treatment of previously treated unresectable or metastatic HER2-mutant NSCLC in more than 45 countries, including the US, Japan and across the EU.