The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending Enhertu (trastuzumab deruxtecan) for approval in the EU as a monotherapy for adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior treatment and have no satisfactory treatment options, according to an announcement from Daiichi Sankyo. The recommendation covers a tumor-agnostic population, potentially making Enhertu the first HER2-directed therapy approved for a tumor-agnostic indication in the EU.
The CHMP opinion will now be reviewed by the European Commission, which holds the authority to grant marketing authorizations across EU member states. Daiichi Sankyo (TSE: 4568), headquartered in Tokyo, and its collaborator AstraZeneca (LSE/STO/NYSE: AZN) are jointly developing and commercializing the asset.
Clinical evidence supporting the recommendation
The CHMP based its positive opinion on data from three Phase II trials: DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02, each evaluating Enhertu at 5.4 mg/kg in previously treated patients with centrally or locally confirmed HER2-positive tumors.
In DESTINY-PanTumor02, a global, multicenter, open-label study enrolling patients with biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, or other tumors, Enhertu produced a confirmed objective response rate (ORR) of 51.4% (95% CI: 41.7–61.0) and a median duration of response (DOR) of 14.2 months in 111 HER2-positive (IHC 3+) patients. In DESTINY-Lung01, which evaluated the drug in HER2-overexpressing non-small cell lung cancer, a confirmed ORR of 52.9% (95% CI: 27.8–77.0) and a median DOR of 6.9 months were observed in 17 IHC 3+ patients. In DESTINY-CRC02, a randomized two-arm Phase II trial in HER2-positive colorectal cancer, the confirmed ORR was 46.9% (95% CI: 34.3–59.8) with a median DOR of 5.5 months among 64 IHC 3+ patients.
The safety profile across the three trials was described by the company as consistent with prior Enhertu clinical experience. In DESTINY-PanTumor02, the most common grade 3 or higher drug-related adverse events were neutropenia and anemia, each occurring in 10.9% of patients. Interstitial lung disease or pneumonitis, a recognized risk with this drug class, was observed in 10.5% of patients, with three grade 5 events reported. Rates were lower in DESTINY-CRC02, where all ILD or pneumonitis events were grade 1 or 2.
Scientific and competitive context
HER2 overexpression has been a validated therapeutic target in breast, gastric, and salivary gland cancers for over two decades, but its role across a broader range of solid tumors has only recently been systematically explored. In tumor types such as biliary tract, colorectal, cervical, and pancreatic cancer, HER2 testing is not routinely performed in the EU, and no HER2-directed therapies have previously been authorized for these indications in that region.
The CHMP recommendation positions Enhertu within a tumor-agnostic framework, a relatively recent regulatory approach that defines eligibility by molecular marker rather than tissue of origin. In the US, the FDA granted accelerated approval to Enhertu for HER2-positive solid tumors in 2024, and the drug has since received approval in more than 15 countries for this indication. The EU recommendation, if converted to a full marketing authorization by the European Commission, would extend that reach to one of the largest regulated pharmaceutical markets globally.