DualityBio and BioNTech take on Enhertu in HER2 low

Just four months after signing a tie-up worth $170m up front, DualityBio and BioNTech have taken the lead asset in that deal, DB-1303, into a phase 3 study. DB-1303 is an antibody-drug conjugate targeting HER2, the same modality as that of Daiichi Sankyo/AstraZeneca’s juggernaut Enhertu, which has already sold over $1bn globally in the first half of this year. The phase 3 study of DB-1303, named Dynasty-Breast02, is notable for enrolling patients with breast cancer that expresses only low levels of HER2; this setting represents a major label expansion for Enhertu, which after being approved in HER2-positive breast cancer then got the US green light in HER2-low disease on the basis of the Destiny-Breast04 trial. Several competing companies are known also to be pursuing the HER2-low space, including Seagen/RemeGen with disitamab vedotin and Byondis with SYD985. According to clinicaltrials.gov Dynasty-Breast02 uses the same definition of HER2-low as Destiny-Breast04, namely an immunohistochemistry (IHC) score of 1+, or IHC2+ with a negative in-situ hybridisation score (ISH-). The DualityBio trial aims to recruit the first of its planned 466 patients in November.

ADCs targeting HER2 in phase 2 development or above

Note: *solid tumours; all others are in breast cancer. Source: OncologyPipeline.