AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the European Union (EU) as monotherapy for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumors have an activating HER2 (ERBB2) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy.

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

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the DESTINY-Lung02 Phase II trial presented at the IASLC 2023 World Conference on Lung Cancer and simultaneously published in the Journal of Clinical Oncology

In the trial, Enhertu 5.4mg/kg demonstrated 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), in patients with previously treated advanced or metastatic HER2-mutant (HER2m) NSCLC. One (1.0%) complete response (CR) and 49 (48.0%) partial responses (PR) were observed. The median duration of response (DoR) was 16.8 months (95% CI 6.4-not estimated [NE]).

Martin Reck, MD,PhD,Head of the Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany, said: “HER2-mutant non-small cell lung cancer is more commonly diagnosed in patients who are younger and female, and there are limited treatment options which often results in a poor prognosis. Enhertu is the first HER2-directed therapy to demonstrate strong and durable results for these patients, and this EU approval marks an important step forward in how the disease can be treated.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Understanding the molecular drivers behind a lung cancer diagnosis is critical, and while there are now targeted options for many patients, those with HER2-mutant non-small cell lung cancer have had few treatment options, none of which have been approved to treat their specific type of lung cancer. Enhertu is the first HER2-directed option approved for HER2-mutant disease and confirms the relevance of HER2 as a target in lung cancer.”

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said: “Since our initial approval of Enhertu for metastatic breast cancer in the EU more than two years ago, we have remained committed to bringing this innovative antibody drug conjugate to more patients with HER2-targetable tumors, especially those that have previously not been eligible for treatment with a HER2-directed therapy. With today’s news, Enhertu is the first antibody drug conjugate approved for lung cancer in the EU and is now approved in three different tumour types.”

The safety profile of Enhertu in the DESTINY-Lung02 trial was consistent with previous clinical trials with no new safety signals identified.