PURPOSE: Triple-negative breast cancer (TNBC) is a heterogeneous disease with high recurrence rates and poor prognosis, often requiring multiple therapies. BEGONIA was a phase Ib/II, multiarm, platform study evaluating the safety and efficacy of first-line treatment combinations with durvalumab (anti-PD-L1 antibody) for locally advanced unresectable/metastatic TNBC (mTNBC; NCT03742102). Here, we report results of three treatment arms. PATIENTS AND METHODS: Eligible female participants (≥18 years with untreated, unresectable, locally advanced/mTNBC) received durvalumab plus paclitaxel or were randomized to this treatment in combination with capivasertib (pan-AKT inhibitor) or oleclumab (anti-CD73 antibody). The primary objective was safety and tolerability; secondary endpoints included objective response rate (ORR). RESULTS: Twenty-three patients received durvalumab plus paclitaxel, 31 capivasertib combination, and 33 oleclumab combination. Maximum grade 3/4 adverse events occurred in 10/23 (43.5%), 25/31 (80.6%) and 8/33 (24.2%) patients in the durvalumab plus paclitaxel, capivasertib-combination, and oleclumab-combination arms, respectively. Confirmed ORR (95% confidence interval) was 56.5% (34.5-76.8) with durvalumab plus paclitaxel, 54.8% (36.0-72.7) with capivasertib combination, and 51.5% (33.5-69.2) with oleclumab combination. Responses were observed across biomarker subgroups, including PD-L1, PIK3CA/AKT1/PTEN alterations, and CD73, with a trend for improved activity in the PD-L1-positive subgroups. CONCLUSIONS: These findings support the clinical activity and tolerability of durvalumab plus paclitaxel in locally advanced unresectable/mTNBC, as expected for an immune checkpoint inhibitor in combination with chemotherapy. Addition of capivasertib or oleclumab to this treatment combination showed no substantial additional benefit. PD-L1 expression was associated with enhanced antitumor activity across all arms.