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
Project | Company | Key trials |
---|---|---|
Approved | ||
Kadcyla | Roche | NCT00829166 |
Enhertu | Daiichi Sankyo/ AstraZeneca | NCT03734029 |
Phase 3 | ||
BAT8001 | Bio-Thera Solutions | NCT04185649 |
Disitamab vedotin/ RC48 | Seagen/ RemeGen | NCT03500380 |
DP303c | CSPC Pharmaceutical | NCT05901935 |
MRG002 | Lepu Biopharma | NCT04924699 |
Trastuzumab duocarmazine/ SYD985 | Byondis | NCT03262935 |
Trastuzumab monomethyl auristatin F/ FS-1502 | Iksuda/ Fosun | NCT05755048 |
Trastuzumab rezetecan/ SHR-A1811 | Luzsana (Jiangsu HengRui) | NCT05424835 |
DB-1303/ BNT323 | DualityBio/ BioNTech | NCT06018337 |
Phase 2 | ||
ARX788 | Ambrx | NCT04829604 |
GQ1001 | GeneQuantum Healthcare | NCT05575804 |
BDC-1001 | Bolt Biotherapeutics | NCT04278144* |
IBI354 | Innovent Biologics | NCT05636215* |
Trastuzumab botidotin/ A166 | Klus (Kelun) | NCT03602079* |
Note: *solid tumours; all others are in breast cancer. Source: OncologyPipeline.
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