AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been approved in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumours who have received prior treatment and who have no satisfactory treatment options.
The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and is based on results from a subgroup of patients with HER2-positive (IHC 3+) tumours across three Phase II trials, DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02.
Benedikt Westphalen, MD, Head of the Precision Oncology Program, Comprehensive Cancer Center of the University of Munich, Germany, said: "HER2 overexpression occurs across multiple tumour types and is associated with aggressive disease and a poor prognosis. Until now, HER2-directed therapies were only available for specific tumour types. The approval of trastuzumab deruxtecan as a tumour-agnostic therapy opens a new treatment option for patients with HER2-positive cancers regardless of where the tumour originated."
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "Precision medicine is reshaping cancer care by helping inform treatment decisions based on the molecular and biological characteristics of a patient's disease. Enhertu is already approved in breast, gastric, and lung cancers, and with this approval, clinicians may now consider Enhertu for patients with HER2-positive status across multiple additional tumour types. This highlights the importance of biomarker testing to identify eligible patients and ensure that those with HER2-positive disease are considered for targeted treatment."
Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said: "This approval of Enhertu marks a significant milestone in the EU for patients with HER2-positive metastatic solid tumours and establishes the first tumour-agnostic indication for a HER2-directed therapy and antibody drug conjugate in the region. Enhertu is now approved for six indications in the EU, which demonstrates our commitment to advancing innovative medicines in areas of high unmet need to patients with cancer."
In the DESTINY-PanTumor02 Phase II trial, Enhertu demonstrated a confirmed objective response rate (ORR) of 52.3% (95% confidence interval [CI] 42.6-61.8) and median duration of response (DOR) of 21.1 months (95% CI 10.6-25.0) in patients with previously treated centrally or locally assessed IHC 3+ solid tumours (n=111) including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic or other tumours. In DESTINY-Lung01, Enhertu demonstrated a confirmed ORR of 52.9% (95% CI 27.8-77.0) and median DOR of 6.9 months (95% CI 4.0-9.8) in patients with previously treated centrally confirmed IHC 3+ non-small cell lung cancer (NSCLC) (n=17). In DESTINY-CRC02, Enhertu demonstrated a confirmed ORR of 46.9% (95% CI 34.3-59.8) and median DOR of 5.5 months (95% CI 4.2-8.1) in patients with previously treated centrally confirmed IHC 3+ colorectal cancer (n=64).
The safety profile of Enhertu was based on a pooled analysis of patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours enrolled in DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and DESTINY-Breast01, and was consistent with previous clinical trials, with no new safety concerns identified.
Enhertu has received a tumour agnostic indication in the US and other countries based on the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
Additional regulatory submissions for Enhertu are under review in the EU, including in combination with pertuzumab for the 1st-line treatment of patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer based on data from the DESTINY-Breast09 Phase III trial and for patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease after neoadjuvant HER2-targeted treatment based on data from the DESTINY-Breast05 Phase III trial.
Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
