ENHERTU^® (trastuzumab deruxtecan) has been approved in the European Union (EU) as a 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 Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN).

The approval by the European Commission (EC) follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) and is based on results from the DESTINY-Lung02 phase 2 trial presented at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer and simultaneously published in the Journal of Clinical Oncology.

In DESTINY-Lung02, ENHERTU (5.4 mg/kg) demonstrated a confirmed objective response rate (ORR) of 49.0% (95% confidence interval [CI]: 39.0-59.1) in patients with previously treated advanced or metastatic HER2 mutant NSCLC as assessed by blinded independent central review (BICR). 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 estimable [NE]).

“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,” said Professor Martin Reck, MD, Head of Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Germany. “ENHERTU is the first HER2 directed therapy to demonstrate strong and durable results for these patients, and this approval in the EU marks an important step forward in how the disease can be treated.”

“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,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “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 tumor types.”

“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,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. “ENHERTU is the first HER2 directed option approved for HER2 mutant disease and confirms the relevance of HER2 as a target in lung cancer.”

In DESTINY-Lung02, the safety profile of ENHERTU was consistent with other trials of ENHERTU with no new safety signals observed. Grade 3 or grade 4 treatment-related adverse events from a pooled safety analysis of patients treated with at least one dose of ENHERTU 5.4 mg/kg across multiple tumor types in clinical studies (n=1,449) included neutropenia (17.0%), anemia (9.5%), fatigue (8.4%), leukopenia (6.4%), nausea (5.9%), thrombocytopenia (5.0%), lymphopenia (4.8%), hypokalemia (3.8%), transaminases increased (3.6%), vomiting (2.7%), diarrhea (2.0%), decreased appetite (1.7%), pneumonia (1.4%) and ejection fraction decreased (1.1%). Grade 5 adverse reactions occurred in 1.4% of patients, including interstitial lung disease (1.0%).