Survival results for datopotamab deruxtecan in TROPION- Breast01 did not achieve statistical significance versus chemotherapy

On September 23^rd, AstraZeneca (AZ) and Daiichi Sankyo (DS) announced that the Phase 3 TROPION-Breast01 trial evaluating datopotamab deruxtecan (Dato-DXd, TROP2-ADC) vs. TPC in 2L+ HR+/HER2- mBC did not achieve statistical significance in the final OS analysis. 

• AZ/DS stated that data will be presented at a “forthcoming medical meeting”, potentially SABCS 2024, and will also be shared with regulatory authorities currently reviewing applications for this indication
  • Interestingly, while previous press release on the PFS benefit mentioned positive trend in OS which numerically favored Dato-DXd without statistical significance, this press release did not mention any specifics around the OS data
  • The companies noted that  the approval of multiple ADCs during the trial, including T-DXd (Enhertu, HER2-ADC) “is likely to have affected survival results.” though previous data cuts had relatively low rates of crossover
  • Dato-DXd is still expected to have a regulatory path forward if OS data is not deemed detrimental; However, ex-US reimbursement may be challenging without OS benefit 
  • in March 2024, the MAA based on TROPION-Breast01 was validated by the EMA; in April 2024, the BLA for the same indication was accepted by the US FDA with a PDUFA date of January 29, 2025
• If approved, Dato-DXd would be to be the second-to-market TROP2-ADC in HR+/HER2- mBC after Trodelvy; However, this miss on OS, following their recent miss on NSCLC OS, will likely impact Dato-DXd’s competitive threat given the potential negative halo on Dato-DXd for both regulatory authorities and HCPs