FDA accetta la domanda di registrazione per Datopotamab deruxtecan per il trattamento del tumore al seno HR+/HER2- in 2L+

Breast Cancer:

• FDA filing acceptanceof Datopotamab deruxtecan (Dato-DXd; TROP2 ADC) based on the results of the Phase 3 TROPION-Breast01 trial in 2L+ HR+/HER2- mBC, expected in Q1 2024, has been accepted on April with a PDUFA date of Jan 29, 2025. (AZ PR link, DS PR link)
• Of note, the PDUFA date of Jan 29, 2025 appears to indicate that Dato-DXd will undergo a standard review timeline
• In their PRs, the companies reiterated that additional regulatory submission in other global geographies for Dato-DXd in HR+/HER2- mBC are currently underway; EMA submission was for Dato-DXd was accepted in early March 2024.
• With this submission, Dato-DXd is now positioned to be the second-to-market TROP2-ADC behind Trodelvy
• Data readout for Phase 3DESTINY-Breast06 trial of trastuzumab deruxtecan (T-DXd, HER2-ADC) in 2L+ chemo-naïve HR+/HER2-low/ultralow mBC is now expected in Q2/Q3 2024 (JP H1 FY2024) [Previously Q4 2023-Q1 2024 (JP H2 2023)]
  • If positive, the movement of T-DXd into the HR+/HER2-ultralow setting would increase percentage HR+ patients eligible for T-DXd beyond what was established through DESTINY-Breast04 and into the chemo-naïve population, competing with Trodelvy’s Phase 3 ASCENT-07 study
• Data readout for the Phase 3TROPION-Breast02 trial of Dato-DXd in 1L PD-L1 ineligible TNBC continues to be expected for Q2 2024 – Q1 2025 (JP FY2024)
  • Potential for Dato-DXd moving into 1L TNBC would position it to directly compete with Trodelvy’s Phase 3 ASCENT-03 trial
  • While TROPION-Breast01 demonstrated higher numerical mPFS compared to Trodelvy in TROPICS-02 (mPFS: 6.9 mo vs 5 mo), this is likely due to the study population being less-heavily pre-treated given similar HR between the two trials (HR: 0.63 vs 0.66)
  • As Dato-DXd has the ability to enter the HR+/HER2- mBC setting in an early LoT compared to Trodelvy’s current label, it remains a high competitive threat; although, Trodelvy may have a first-to-market advantage until mature OS or other differentiating data is presented for Dato-DXd

NSCLC:

• Dato-DXd FDA filing acceptance for 2L/3L mNSCLC continues to be expected in Q1 2024 (JP Q4 2023)