BioNTech and DualityBio branch out
Until now BioNTech’s phase 3 efforts with its DualityBio-partnered anti-HER2 ADC BNT323 have mirrored those of its key rival, Daiichi Sankyo/AstraZeneca’s juggernaut Enhertu. This is about to change, however: BNT323’s latest pivotal study, just unveiled on the clinicaltrials.gov registry, concerns endometrial cancer. Not only is Enhertu not in phase 3 development in this cancer type, it barely appears to have been tested in this setting at all. OncologyPipeline reveals that one relevant trial, an uncontrolled phase 2 study called Statice, was carried out in Japan; this tested Enhertu in HER2-positive uterine carcinosarcoma patients who had received chemotherapy, and showed ORRs of 55% in 22 HER2-high patients and 70% in 10 HER2-low patients, with one subject experiencing grade 3 pneumonitis/interstitial lung disease. BioNTech licensed BNT323 from DualityBio for $170m up front a year ago, and the new phase 3 study will compare the ADC against physician’s choice chemo in 468 patients with HER2-positive endometrial cancer progressed on platinum therapy.
A battle of two HER2 ADCs
Enhertu | DB-1303/ BNT323 | |
---|---|---|
Daiichi Sankyo/ AstraZeneca | DualityBio/ BioNTech | |
Payload | DXd, topo1 inhibitor | P1003, topo1 inhibitor |
Linker | Cathepsin cleavable | Protease cleavable |
DAR^ | 7-8 | 8 |
2nd-line HER2+ve breast cancer | ||
Ph3 trial | Destiny-Breast03* | Dynasty-Breast01 |
Design/data | HR=0.64 for OS, HR=0.28 for PFS, vs Kadcyla | Vs Kadcyla |
HER2-low breast cancer | ||
Ph3 trial | Destiny-Breast04* | Dynasty-Breast02 |
Design/data | HR=0.64 for OS, HR=0.51 for PFS, vs chemo in ER+ve cohort | Vs chemo |
2nd-line HER2+ve endometrial cancer | ||
Ph3 trial | None | ENGOT-en25 |
Design/data | Vs chemo |
Notes: ^drug-to-antibody ratio; *approved use. Source: OncologyPipeline & prescribing information.
On 5 April 2024 Enhertu was approved for second-line HER2-positive solid tumours, a use that would be expected to include second-line HER2-positive endometrial cancer; however, this is on an accelerated basis, based on remission rates in the phase 2 Destiny-Pantumor02 study and two other mid-stage trials.
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