379MO Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Updated results from BEGONIA, a phase Ib/II study

BEGONIA (NCT03742102) is an ongoing 2-part, open-label platform study in 1L a/mTNBC, evaluating D, an anti–PD-L1 antibody, plus novel therapies, including Dato-DXd, an antibody-drug conjugate made of a anti-TROP2 antibody covalently linked via a cleavable linker to a topoisomerase I inhibitor payload. Early data from BEGONIA Arm 7, Dato-DXd + D, showed promising responses. Updated results, including response duration (DoR), are reported. Patients (pts) with unresectable a/mTNBC eligible for 1L treatment were enrolled, regardless of PD-L1/TROP2 expression, and received Dato-DXd 6 mg/kg IV + D 1120 mg IV Q3W until progression or unacceptable toxicity. PD-L1, assessed by the VENTANA PD-L1 (SP263) Assay, was high if ≥10% of the tumor area was populated by PD-L1–expressing tumor or immune cells. Primary endpoints were safety and tolerability. Secondary endpoints included investigator-assessed ORR, PFS (RECIST v1.1), and DoR. As of 2 Feb 2023, 62 pts received Dato-DXd + D (29 ongoing). Median follow-up was 11.7 (range 2–20) months (mos). At baseline, median pt age was 53 years; 60% had visceral metastases; 87% had PD-L1–low expression. Confirmed ORR was 79% (95% CI, 67–88); 6 (10%) pts had complete and 43 (69%) had partial responses. Response to treatment was irrespective of PD-L1 expression level. Median DoR was 15.5 mos (95% CI, 9.9–not calculable [NC]). Median PFS was 13.8 mos (95% CI, 11–NC). Nausea and stomatitis were the most common adverse events (AEs; 40 [65%] each). Any Grade (G) 3/4 AEs occurred in 35 (57%) pts and serious AEs in 14 (23%). Low rates of anemia (9 [15%]), diarrhea (8 [13%]), and neutropenia (3 [5%]) occurred. Adjudicated treatment-related interstitial lung disease/pneumonitis occurred in 3 (5%) pts (2 G2; 1 G1). No deaths due to treatment-related AEs occurred. 10 (16%) pts discontinued any study drug due to AEs. No new safety signals were reported. Dato-DXd combined with D continues to demonstrate manageable safety and compelling high, durable response rates in 1L a/mTNBC. Further investigation is warranted. Translational data analysis is ongoing. Funding: AstraZeneca/Daiichi Sankyo.