New Merck Phase 3 trial (TroFuse-011) assessing sacituzumab tirumotecan ± pembrolizumab in 1L metastatic Triple Negative Breast Cancer (mTNBC)

On February 24^th 2025, Merck listed a new Phase 3 TroFuse-011 trial assessing sacituzumab tirumotecan (sac-TMT, SKB264, MK-2870; TROP2-ADC) ± pembrolizumab (Keytruda; anti-PD-1) vs treatment of physician’s choice (TPC) in PD-L1 CPS <10 1L mTNBC (N=1000; PCD: May 2030; SCD: May 2030).

• This marks the second Merck-sponsored global, pivotal trial for sac-TMT in TNBC, following the initiation of TroFuse-012 in eTNBC in Q2 2024
  • Trial sites are yet to be listed; however, global sites are expected
  • Trial is expected to initiate on March 24^th 2025 and is currently “not yet recruiting”
• The three arm trial will evaluate sac-TMT ± pembrolizumab vs. TPC in patients that have a PD-L1 CPS < 10, highlighting belief of sac-TMT as a best in class TROP2 ADC, its potential as part of a combination regimen and its ambitions to maximize pembro usage in TNBC patients
  • The current trial is the first registrational trial to evaluate ADCs + PD-L1 in 1L TNBC within the PD-(L)1 negative population (CPS<10)
• Primary outcomes are PFS ( Sac-TMT vs TPC /Sac-TMT+pembro vs TPC ) and OS (Sac-TMT vs TPC), with key secondary outcomes assessing both safety and efficacy measures
• The trial likely seeks to differentiate Sac-TMT from other TROP2-ADCs by studying a combination in 1L mTNBC that is not explicitly addressed by current registrational Trodelvy or Datroway trials
  • While TB-02 and ASCENT-03 would be the closest comparator studies in terms of patient populations (PD-L1 negative/ ineligible), neither includes a PD-(L)1 combination arm, which may present an opportunity for Sac-TMT to differentiate itself from its other in-class competitors
  • However, as a significantly late-to-market entrant in the 1L mTNBC space, sac-TMT will need to show significant differentiation against Trodelvy and Datroway