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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/ AstraZenecaDualityBio/ BioNTech
PayloadDXd, topo1 inhibitorP1003, topo1 inhibitor
LinkerCathepsin cleavableProtease cleavable
DAR^7-88

 
2nd-line HER2+ve breast cancer
Ph3 trialDestiny-Breast03*Dynasty-Breast01
Design/dataHR=0.64 for OS, HR=0.28 for PFS, vs KadcylaVs Kadcyla

 
HER2-low breast cancer
Ph3 trialDestiny-Breast04*Dynasty-Breast02
Design/dataHR=0.64 for OS, HR=0.51 for PFS, vs chemo in ER+ve cohortVs chemo

 
2nd-line HER2+ve endometrial cancer
Ph3 trialNoneENGOT-en25
Design/dataVs 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.

Tags

Molecular Drug Targets