EU Approves Enhertu as First HER2 Tumor-Agnostic Therapy for Advanced Solid Tumors

The European Commission has approved Enhertu (trastuzumab deruxtecan) as a monotherapy for adults with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior treatment and have no satisfactory therapeutic options. The decision makes Enhertu the first HER2-directed tumor-agnostic therapy and antibody-drug conjugate (ADC) approved in the European Union, expanding access to targeted treatment beyond cancers defined by their tissue of origin.

The approval follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) and is based on evidence from three Phase II studies: DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02.

Expanding Precision Oncology Beyond Tumor Origin

HER2 is a growth-promoting receptor that is overexpressed in several solid tumors and is often associated with aggressive disease and poor clinical outcomes. While HER2-targeted therapies have long been available for breast, gastric, and selected biliary cancers, patients with HER2-positive tumors arising from other organs previously had limited targeted treatment options.

Enhertu is a HER2-directed antibody-drug conjugate that combines a monoclonal antibody targeting HER2 with Daiichi Sankyo’s DXd topoisomerase I inhibitor payload through a cleavable linker. After binding to HER2-expressing tumor cells, the ADC delivers its cytotoxic payload directly into cancer cells while limiting systemic exposure.

Phase II Trials Show Durable Responses Across Multiple Tumor Types

The approval is supported by clinically meaningful efficacy observed across three Phase II clinical trials.

In DESTINY-PanTumor02 (NCT04482309), which enrolled 111 patients with previously treated HER2-positive (IHC 3+) solid tumors, Enhertu achieved a confirmed objective response rate (ORR) of 52.3% with a median duration of response (DOR) of 21.1 months. The study included patients with biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and other solid tumors.

Among patients with HER2-positive non-small cell lung cancer in DESTINY-Lung01 (NCT03505710) (n=17) Enhertu produced a confirmed ORR of 52.9% and a median DOR of 6.9 months.

In DESTINY-CRC02 (NCT04744831), involving 64 patients with HER2-positive colorectal cancer, the ADC demonstrated a confirmed ORR of 46.9% with a median DOR of 5.5 months.

Across all three studies, the responses supported the use of HER2 status as a biomarker for treatment selection regardless of tumor origin.

Safety Profile Remained Consistent

The European approval also relied on a pooled safety analysis from DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02, and DESTINY-Breast01. The overall safety profile remained consistent with previous clinical experience, and investigators reported no new safety signals, reinforcing the established benefit-risk profile of Enhertu in HER2-positive cancers.

Biomarker Testing Becomes Increasingly Important

Commenting on the approval, Benedikt Westphalen, MD, Head of the Precision Oncology Program at the Comprehensive Cancer Center, University of Munich, said the decision broadens access to HER2-directed treatment for patients with HER2-positive cancers regardless of where the tumor originated.

AstraZeneca highlighted that the approval reflects the growing role of precision medicine and reinforces the importance of routine biomarker testing to identify patients who may benefit from HER2-targeted therapies. Daiichi Sankyo described the authorization as a major milestone that establishes the first HER2-directed tumor-agnostic indication in the European Union and expands Enhertu’s approved indications in the region to six.

Path Forward

Enhertu has already received tumor-agnostic approval in the United States and several other markets. AstraZeneca and Daiichi Sankyo continue to expand the drug’s clinical development program across multiple HER2-expressing cancers.

Additional European regulatory submissions remain under review, including Enhertu in combination with pertuzumab for first-line HER2-positive metastatic breast cancer based on the Phase III DESTINY-Breast09 trial, and for patients with residual invasive HER2-positive breast cancer following neoadjuvant HER2-targeted therapy based on the Phase III DESTINY-Breast05 study. Following the EU approval, AstraZeneca will make a $25 million milestone payment to Daiichi Sankyo under their collaboration agreement.

Reference

Enhertu approved in the EU as first tumour agnostic HER2-directed therapy and antibody drug conjugate for patients with previously treated HER2-positive metastatic solid tumours

Enhertu Approved in the EU as First Tumor Agnostic HER2 Directed Therapy and Antibody Drug Conjugate for Patients with Previously Treated HER2 Positive Metastatic Solid Tumors