Dato-DXd (TROP2 ADC) + durvalumab (PD-L1) drives ~80% ORR and 14-mo mPFS in 1L metastatic TNBC (BEGONIA)

Dato-DXd is a TROP2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor payload (deruxtecan), combined here with durvalumab (anti–PD-L1) as first-line therapy in unresectable locally advanced/metastatic TNBC in the Phase Ib/II BEGONIA platform (Simon 2-stage; Arms 7–8; NCT03742102). At the 29 Nov 2024 cut-off, Arm 7 enrolled all-comers (n=62) and reported cORR 79.0% (95% CI 66.8–88.3), median DoR 17.6 months, median PFS 14.0 months, and median OS not reached with 35.0 months median follow-up; Arm 8 restricted to locally PD-L1-high tumors (n=33) and showed cORR 81.8% with immature DoR/PFS given short follow-up (median 10.7 months; 8.3 months in censored patients). Numerically, Arm 7’s 14.0-month mPFS is well above historical 1L PD-1/PD-L1+chemo benchmarks in PD-L1–selected TNBC (e.g., KEYNOTE-355 CPS≥10 mPFS 9.7 months; IMpassion130 PD-L1+ mPFS 7.4 months), though those were randomized chemo-backbone trials and BEGONIA is non-randomized with a small n; safety was described as “manageable” with no new signals versus prior studies (but grade ≥3 AE rates and key ADC toxicities were not provided in this abstract).