80 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 1b/2 BEGONIA Study

Background

BEGONIA (NCT03742102) is a 2-part, open-label platform study evaluating the safety and efficacy of durvalumab, an anti-PD-L1 antibody, combined with novel therapies as first-line treatment for advanced/metastatic triple-negative breast cancer (TNBC). We report updated data for durvalumab in combination with datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate, from arm 7 and the first report from arm 8.

Methods

Patients with unresectable advanced/metastatic TNBC eligible for first-line treatment were enrolled. Arm 7 included patients regardless of tumor PD-L1 expression level. Arm 8 enrolled patients with PD-L1-high tumors, as determined by immunohistochemistry assay (local test). Patients received Dato-DXd 6 mg/kg IV plus durvalumab 1120 mg IV every 3 weeks until progression or unacceptable toxicity. Primary end points were safety and tolerability. Secondary end points included confirmed objective response rate (cORR) assessed by investigator, duration of response (DoR) and progression-free survival (PFS) per RECIST 1.1.

Results

At data cut-off (November 29, 2024), 62 patients had received Dato-DXd plus durvalumab (19.4% ongoing study treatment) in arm 7 and 33 patients received Dato-DXd plus durvalumab (45.4% ongoing study treatment) in arm 8. In arm 7 (median follow-up 35.0 months), cORR was 79.0% (95% CI, 66.8-88.3). Median DoR was 17.6 months (95% CI, 10.5-27.3). Median PFS was 14.0 months (11.0-21.1). In arm 8 (median follow-up of 10.7 months), cORR was 81.8% (95% CI, 64.5-93.0). Median DoR and median PFS could not be accurately determined due to the short follow-up period. Safety data are summarized in the Table. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 3 (5%) patients in arm 7 (grade 2: n = 2; grade 1: n = 1) and 1 (3%) patient in arm 8 (grade 2).

Conclusions

In first-line advanced/metastatic TNBC, the combination of Dato-DXd plus durvalumab continued to demonstrate robust antitumor activity across both arms. The safety profile was manageable with no new safety signals.

Previously presented at ESMO 2025 by Peter Schmid et al. Abstract 555MO. Reused with permission.

This trial is sponsored by AstraZeneca. In July 2020, Daiichi-Sankyo entered into a global development and commercialization collaboration with

AstraZeneca for datopotamab deruxtecan (Dato-DXd). Medical writing support for the development of this abstract, under the direction of the authors,

was provided by Lydia Hallam of Ashfield MedComms (London, UK), an Inizio company, in accordance with Good Publication Practice (GPP) guidelines

(http://www.ismpp.org/gpp-2022), and was funded by AstraZeneca.