Merck Phase 3 trial evaluating adjuvant sacituzumab tirumotecan + pembrolizumab (Keytruda) Vs treatment of physician’s choice (TPC, pembrolizumab +/- capecitabine) in eTNBC

Merck listed a new Phase 3 trial evaluating adjuvant sacituzumab tirumotecan (sac-TMT, MK-2870/SKB264; TROP2 ADC) + pembrolizumab (Keytruda, anti-PD-1) vs treatment of physician’s choice (TPC, pembrolizumab +/- capecitabine) in eTNBC who received neoadjuvant therapy and did not achieve pCR .

MK-2870 is a key in-class competitor for ongoing ASCENT-05 study 

Highlights and Implications:

• This marks the second Merck-sponsored global, pivotal trial for MK-2870 in breast cancer, following the recently listed Phase 3 MK-2870-010 trial in post ET/ chemo-naïve HR+/HER2- mBC
• The trial specifically includes patients who have had neoadjuvant treatment based on the KEYNOTE-522 regimen (pembrolizumab + chemotherapy) followed by surgery according to NCCN treatment guidelines for TNBC
  • It appears that Merck aims to provide an ADC option for the patient population with residual disease following neoadjuvant pembrolizumab + chemotherapy beyond pembrolizumab +/- capecitabine
• The trial also specifically excludes patients with a "history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing" likely due to the ocular toxicities observed in earlier phase studies
• The primary outcome is iDFS; key secondary outcomes include OS, distant recurrence-free survival (DRFS), and AEs
• It remains to be seen how Merck aims to difference MK-2870 in eTNBC, given it will likely be a 3rd to market TROP2-ADC to be investigated in this setting ;Previously published data in BC from earlier studies has not indicated significant areas of differentiation for MK-2870 from either Dato-DXd or Trodelvy
  • Upcoming P3 data from the Kelun sponsored/China study in 3L+ TNBC  will likely provide more insight into MK-2870, in particular its safety profile
  • Merck may also look leverage its portfolio synergies and experience with Keytruda in these combination regimens