AstraZeneca (LSE/STO/NYSE: AZN) and Daiichi Sankyo have received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommending Enhertu (trastuzumab deruxtecan) for a new indication approval. The committee gave the nod for Enhertu as a monotherapy in adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior treatment and have no satisfactory alternative options. If going on to formalize approval from the EMA, Enhertu would be the first tumour-agnostic HER2-directed therapy and antibody drug conjugate (ADC) in the EU.
The CHMP recommendation covers Enhertu administered at 5.4 mg/kg as a monotherapy. The filing seeks approval across solid tumour types defined by HER2 overexpression at the IHC 3+ threshold, regardless of histological origin. The target population is patients who have already received prior systemic treatment and for whom no satisfactory treatment options remain — a definition that, in practice, encompasses patients with HER2-overexpressing biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, colorectal, and other solid tumours for which no approved HER2-directed therapy currently exists in the EU.
The positive CHMP opinion now moves to the European Commission for a formal marketing authorisation decision, which typically follows within two months of the committee recommendation.
The CHMP based its positive opinion on data from the Phase II DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02 studies in patients with centrally confirmed HER2 IHC 3+ tumours. Across the three studies, confirmed ORRs ranged from 46.9% to 52.9%, with median DOR ranging from 5.5 to 14.2 months depending on tumour type. The companies said the safety profile was consistent with prior Enhertu studies and no new safety signals were identified.
The companies said the safety profile of Enhertu across these trials was consistent with prior clinical experience, with no new safety concerns identified.
Originally designed using Daiichi Sankyo's DXd ADC technology, Enhertu consists of a HER2-targeting monoclonal antibody linked via cleavable tetrapeptide-based linkers to a topoisomerase I inhibitor payload, DXd, an exatecan derivative, at a drug-to-antibody ratio of approximately eight. The high payload density and membrane-permeable nature of DXd are thought to enable a bystander killing effect on neighbouring tumour cells, a property that may contribute to activity in tumours with heterogeneous HER2 expression.