First-Line Datopotamab Deruxtecan Plus Durvalumab Demonstrates Clinical Promise Among Patients With Advanced Triple-Negative Breast Cancer
Key Clinical Takeaways
- Design/Population: In the 2-part, open-label phase 1b/2 BEGONIA platform study (n = 95), patients with advanced or metastatic TNBC received Dato-DXd 6 mg/kg plus durvalumab 1120 mg every 3 weeks, regardless of PD-L1 status (arm 7; n = 62) or with high PD-L1 expression (arm 8; n = 33).
- Key Outcomes: Confirmed ORR was 79% in arm 7 and 81.8% in arm 8; grade 3/4 treatment-related adverse events occurred in 48% and 24% of patients, respectively; treatment discontinuations due to adverse events were 19% and 9%.
- Clinical Relevance: Dato-DXd plus durvalumab demonstrated robust antitumor activity and manageable toxicity, supporting further investigation as a first-line option in advanced TNBC.
According to results from the BEGONIA study, first-line datopotamab deruxtecan (Dato-DXd) plus durvalumab demonstrated clinical promise among patients with advanced or metastatic triple-negative breast cancer (TNBC).
These data will be presented by Peter Schmid, MD, PhD, Barts Cancer Institute, London, United Kingdom, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
The 2-part, open-label platform study, BEGONIA, evaluated combination therapy with durvalumab and different novel agents in the firstline setting for patuents with advanced or metastatic TNBC. This final analysis reports updated data from arm 7 and first results from arm 8, both administering durvalumab with Dato-DXd. Between these 2 arms, researchers enrolled 95 patients to receive 6 mg/kg of Dato-DXd plus 1120 mg of durvalumab once every 3 weeks until disease progression or unacceptable toxicity. Patients were categorized into 2 cohorts: regardless of PD-L1 expression (arm 7; n = 62) or patients with high PD-L1 expression (arm 8; n = 33). Primary end points included safety and tolerability. A key secondary end point was confirmed objective response rate (ORR).
At analysis, 19.4% of patients were still on study treatment in arm 7 compared to 45.4% of patients in arm 8. Grade 3/4 treatment-related adverse events occurred in 48% in arm 7 and 24% of patients in arm 8. Serious treatment-related adverse events occurred in 29% and 15% of patients, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 3 patients in arm 7 and 1 patient in arm 8. Treatment discontinuation due to an adverse event was reported in 19% of patients in arm 7 and 9% of patients in arm 8. Adverse events led to 1 death in arm 7 which was deemed unrelated to study treatment. Confirmed ORR was 79% in arm 7 and 81.8% in arm 8.
According to the study authors, the combination of Dato-DXd plus durvalumab “continued to demonstrate robust antitumor activity across both arms.”
Source:
Schmid P, Wang HC, Lynce F, et al. Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment (tx) for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Final results from the phase Ib/II BEGONIA study. Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. 555MO
