The FDA granted Fast Track designation to CytomX Therapeutics’ varsetatug masetecan (Varseta-M; CX-2051), an EpCAM-directed, masked, conditionally activated antibody–drug conjugate (ADC), for relapsed/refractory metastatic colorectal cancer (R/R mCRC). The designation follows phase 1 dose-expansion data from CTMX-2051-101 (NCT06265688). Across prioritized expansion doses, the confirmed objective response rate ranged from 6% to 32%, with disease control rates in the ~84% to 90% range. Median progression-free survival ranged from 5.5 to 7.1 months depending on dose. CytomX plans to initiate a potential registrational study in this population in the first half of 2027. The decision also highlights continued FDA support for ADCs built on tumor-activated Probody masking aimed at improving therapeutic index in hard-to-treat metastatic settings.