First-line datopotamab deruxtecan plus durvalumab for unresectable locally advanced/metastatic TNBC: arms 7 and 8 of phase 1b-2 BEGONIA study

BEGONIA is a multinational phase 1b-2 study evaluating durvalumab (anti-PD-L1) in combination with novel therapies as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). Arms 7 and 8 assessed durvalumab in combination with the TROP2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-DXd). Arm 7 included 62 patients regardless of tumor PD-L1 expression level, and arm 8 included 33 patients with PD-L1-high tumors. Patients received Dato-DXd 6 mg/kg plus durvalumab 1120 mg every three weeks. The safety profile (primary endpoint) was manageable, with no new safety signals versus prior studies. At data cut-off, median follow-up was 35.0 months in arm 7 and 10.7 months in arm 8. In arm 7, confirmed objective response rate was 79.0% (95% CI 66.8-88.3), median duration of response was 17.6 months (10.5-27.3), median progression-free survival was 14.0 months (11.0-21.1), and median overall survival was not reached. In arm 8, cORR was 81.8% (95% CI 64.5-93.0), while median DoR and median PFS were immature. The authors conclude that first-line Dato-DXd plus durvalumab demonstrated substantial and durable antitumor activity in locally advanced unresectable or metastatic TNBC, regardless of PD-L1 status.