BEGONIA Shows No Added Benefit With Capivasertib or Oleclumab Added to Durvalumab Plus Paclitaxel in Advanced Triple-Negative Breast Cancer

Clinical Summary:

• Design/Population: The phase 1b/2 BEGONIA study evaluated first-line durvalumab-based combinations in patients with previously untreated, unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). 
• Key Outcomes: Confirmed objective response rates were 56.5% with durvalumab plus paclitaxel, 54.8% with the addition of capivasertib, and 51.5% with the addition of oleclumab. Neither investigational agent substantially improved activity over durvalumab plus paclitaxel.
• Clinical Relevance: Durvalumab plus paclitaxel demonstrated clinical activity in advanced TNBC, while adding AKT or CD73 inhibition provided no clear additional benefit. Responses occurred across biomarker subgroups, with greater activity observed in patients with PD-L1–positive disease.

Results from the phase 1b/2 BEGONIA trial showed that first-line durvalumab plus paclitaxel produced objective responses in more than half of patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC), while the addition of capivasertib or oleclumab did not appear to substantially improve antitumor activity.

“TNBC is a heterogeneous disease with high recurrence rates and poor prognosis, often requiring multiple therapies,” stated Peter Schmid, MD, PhD, Barts Cancer Institute, London, United Kingdom, and coauthors. “BEGONIA evaluated the safety and efficacy of first-line treatment combinations with durvalumab (anti–PD-L1 antibody) for locally advanced, unresectable/metastatic TNBC.” 

In this trial, eligible patients aged 18 years or older with previously untreated, unresectable locally advanced or metastatic TNBC received durvalumab plus paclitaxel (n = 23) or were randomized to receive the combination with the pan-AKT inhibitor capivasertib (n = 31) or the anti-CD73 antibody oleclumab (n = 33). The primary objective was safety and tolerability, with objective response rate (ORR) assessed as a secondary end point.

At analysis, the confirmed ORR was 56.5% in the durvalumab plus paclitaxel arm, 54.8% in the capivasertib-containing arm, and 51.5% in the oleclumab-containing arm. Responses were observed across biomarker-defined subgroups, including those based on PD-L1 expression, PIK3CA/AKT1/PTEN alterations, and CD73 expression. However, investigators reported a trend toward greater antitumor activity among patients with PD-L1–positive disease across all 3 treatment arms.

Grade 3/4 adverse events occurred in 43.5% of patients in the durvalumab plus paclitaxel arm, 80.6% of patients in the capivasertib-containing arm, and 24.2% of patients in the oleclumab-containing arm. The substantially higher rate observed with the capivasertib combination occurred without a corresponding improvement in ORR.

“These findings support the clinical activity and tolerability of durvalumab plus paclitaxel in locally advanced unresectable/metastatic TNBC, as expected for an immune checkpoint inhibitor in combination with chemotherapy,” concluded Dr Schmid et al. “The addition of capivasertib or oleclumab to this treatment combination showed no substantial additional benefit.” 

Source:

Schmid P, Ma CX, Park YH, et al. Durvalumab plus paclitaxel, with or without capivasertib or oleclumab, in patients with locally advanced/metastatic triple-negative breast cancer. Clin Cancer Res. Published online: June 30, 2026. doi: 10.1158/1078-0432.ccr-25-4417