New single-arm Phase 3b rial evaluating datopotamab deruxtecan (Dato-DXd) monotherapy in post-ET/chemo-naive HR+/HER2- breast cancer (mBC)

AZ/DS have listed a new single-arm P3b TROPION-Breast06 trial evaluating datopotamab deruxtecan (Dato-DXd; TROP2-ADC) monotherapy in post-ET/chemo-naive HR+/HER2- (IHC 0) mBC (N=100; PCD/SCD: Feb 2028)

 Highlights and Implications

• Primary endpoint: PFS (note there is no comparator arm)
• Secondary endpoints include:
  • Incidence of oral mucositis/stomatitis
  • Incidence of ocular events
  • Incidence of Gr ≥3 AEs related to Dato-DXd
  • Efficacy (OS, ORR, DOR, CBR)
• Trial sites are listed across US, EU, China, and Korea
• Based on its small sample of N=100 and lack of a comparator arm, this trial likely aims to generate data for Dato-DXd in HR+/HER2 setting (IHC 0) where T-DXd doesn’t fully cover based on the P3 DB-06 trial (HER2 low/ultra-low)
  • It remains to be seen how regulatory agencies would view data from this trial; however, we believe the current trial design itself does not support a standalone regulatory submission for a potential label extension
  • Biomarker data from TROPION-Breast06 may be leveraged to support the use of Dato-DXd in specific biomarker population
    • Note, tumor biopsy sample from TROPION-Breast06 will be used to assess HER2 and TROP2 expression, and exploratory biomarkers of response

Additional Background

• Dato-DXd is approved for post-CT HR+/HER2- mBC based on statistically significant and clinically meaningful PFS data (HR: 0.63) from the P3 TROPION-Breast01 trial; however the trial did not demonstrate OS benefit (HR: 1.01)
• Dato-DXd is also being evaluated in the following pivotal trials:
  • P3 TROPION-Breast02 in 1L TNBC not candidates for anti-PD-(L)1
  • 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