Datopotamab deruxtecan (Dato-DXd) met dual primary endpoint of OS and PFS in the P3 TROPION-Breast02 in 1L TNBC

On October 6^th 2025, AstraZeneca (AZ) and Daiichi Sankyo (DS) announced positive topline results from the P3 TROPION-Breast02 trial evaluating datopotamab deruxtecan (Dato-DXd, Datroway; TROP2-ADC) in 1L TNBC ineligible for anti-PD-(L)1 therapy. Dato-DXd demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoint of OS and PFS vs investigator’s choice chemotherapy (ICC) and a consistent safety profile

Highlights and Implications

• The dual primary endpoint of OS and PFS was met in the P3 TROPION-Breast02 trial, demonstrating superior benefit compared to ICC
  • The safety profile of Dato-DXd was consistent with previous trials, with no new safety concerns
• The timeline for this topline readout was expected given that DS has been guiding for a Q4 2025 – Q1 2026 (JP H2 FY2025), while AZ has been guiding for a H2 2025 readout
• TROPION-Breast02 competes directly with Trodelvy’s ASCENT-03  in 1L TNBC
  • With filing expected in Q4 2025, potential approval could occur as early as Q2/Q3 2026 which may follow a similar timeline to Trodelvy’s anticipated approval in 1L TNBC
  • Movement of Dato-DXd into 1L TNBC could potentially limit the eligible patient population for Trodelvy in the later LoT, particularly given concerns over sequencing TROP2-directed therapies
  • While positive data may support Dato-DXd’s entry into TNBC, Trodelvy is the first TROP2 ADC demonstrating proven OS in both TNBC and HR+/HER2- patient populations with substantial 5 years of real world experience and over 60K patients treated globally.
  • Positive results from both ASCENT-03 and ASCENT-04 provide a future backbone option for all 1L TNBC populations regardless of PD-L1 status

Additional Background

• Dato-DXd is currently approved for the treatment of HR+/HER2- mBC post-ET and post-CT in the US, EU, and JP, based on positive PFS data from Phase 3 TROPION-Breast01, which were presented at ESMO 2023 and published in the Journal of Clinical Oncology
  • However, the trial failed to meet its OS endpoint (HR: 1.01)
    • AZ and DS have been messaging that OS failure was potentially due to an imbalance in the use of ADCs as subsequent treatments in the experimental vs control arms
• Dato-DXd is also being evaluated in the following pivotal trials:
  • P3 TROPION-Breast03 in combination with durvalumab (Imfinzi, anti-PD-L1) in Stage I-III TNBC without pCR following neoadjuvant therapy  
  • P3 TROPION-Breast04 in combination with durvalumab as a neoadjuvant treatment for eTNBC
  • P3 TROPION-Breast05 in combination with durvalumab in PD-L1+ (CPS≥10) locally recurrent inoperable or metastatic 1L TNBC