The FDA expanded Gilead’s Trodelvy label into front-line triple-negative breast cancer (TNBC), giving TROP2 ADCs a new footing in first-line treatment. The update allows Trodelvy to be used in patients who are ineligible for PD-1/L1 inhibitors regardless of PD-L1 status, and in combination with Keytruda (pembrolizumab) for PD-L1-positive tumors meeting a CPS threshold of at least 10. The approval is backed by two Phase 3 programs. In Ascent-03, Trodelvy reduced the risk of progression or death by 38% versus chemotherapy in PD-(L)1 inhibitor–ineligible patients. In Ascent-04 (Keynote-D19), the Trodelvy plus Keytruda regimen improved progression-free survival by 35% versus Keytruda plus chemotherapy in PD-L1-positive disease. Clinicians now face a widened set of first-line sequencing options for TNBC patients, increasing competitive pressure on other first-line TROP2 ADC efforts. The label breadth may also influence trial enrollment strategies for next-generation TNBC combinations targeting PD-1/L1 pathways.