The approval allows the drug to be used across multiple HER2-positive cancers, regardless of where the tumour originated, for patients who have exhausted other treatment options.

The European Commission has approved AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) for adults with previously treated HER2-positive metastatic or unresectable solid tumours who have no satisfactory treatment options, the companies said.

HER2 is a molecular feature in tumours, and when it is overexpressed, it is associated with aggressive disease and a poor prognosis. While, tumour-agnostic means the medicine is approved on the basis of a tumour’s molecular feature, rather than the organ in which the cancer started.

The approval makes Enhertu the first HER2-directed therapy and the first antibody-drug conjugate to receive a tumour-agnostic indication in the European Union. HER2-positive, or IHC 3+, means the tumour shows high HER2 expression on testing.

The decision follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). It is based on data from three Phase II clinical trials, (DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02)

A Phase II trial evaluates whether a treatment works in patients with a disease while continuing to assess its safety.

Approval based on three clinical trials

The approval covers adult patients with HER2-positive tumours classified as immunohistochemistry (IHC) 3+, whose cancers are unresectable, meaning they cannot be removed by surgery, or metastatic, meaning they have spread to other parts of the body.

In the DESTINY-PanTumor02 Phase II trial, Enhertu achieved a confirmed objective response rate of 52.3% among 111 patients with previously treated HER2-positive solid tumours, including biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers, as well as other tumour types. The median duration of response was 21.1 months.

In the DESTINY-Lung01 trial, the drug showed a confirmed objective response rate of 52.9% in 17 patients with previously treated HER2-positive non-small cell lung cancer, with a median duration of response of 6.9 months.

In the DESTINY-CRC02 trial involving 64 patients with previously treated HER2-positive colorectal cancer, the confirmed objective response rate was 46.9%, with a median duration of response of 5.5 months.

Objective response rate refers to the proportion of patients whose tumours shrink by a predefined amount or disappear following treatment.

Safety findings

According to the companies, the safety assessment pooled data from four clinical trials, including DESTINY-Breast01, and found that the safety profile was consistent with previous studies. No new safety concerns were identified.

Enhertu is an antibody-drug conjugate, a type of targeted cancer therapy that combines an antibody designed to recognise cancer cells with a chemotherapy drug. The antibody delivers the treatment directly to cancer cells to help limit damage to healthy tissue.

Experts highlight broader treatment option

“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,” said Dr Benedikt Westphalen, Head of the Precision Oncology Program at the Comprehensive Cancer Center of the University of Munich, Germany. 

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, said the approval reflected the growing role of precision medicine in cancer treatment.

“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,” he said.

Biomarker testing identifies specific molecular characteristics of a tumour that may help determine whether a patient is likely to benefit from a targeted treatment.

Ken Keller, Global Head of Oncology Business and President and Chief Executive Officer of Daiichi Sankyo, Inc., said the approval establishes the first tumour-agnostic indication in the European Union for both a HER2-directed therapy and an antibody-drug conjugate.

Next regulatory steps

The companies said Enhertu has already received a tumour-agnostic indication in the United States and several other countries based on the same three Phase II studies. They added that additional regulatory submissions remain under review in the European Union.