Durvalumab plus Paclitaxel, with or without Capivasertib or Oleclumab, in Patients with Locally Advanced/Metastatic

Peter Schmid1, Cynthia X Ma2, Yeon Hee Park3

  • 1Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.

Abstract

Insights

First-line durvalumab plus paclitaxel showed clinical activity in triple-negative breast cancer (TNBC). Adding capivasertib or oleclumab did not significantly improve outcomes, though PD-L1 expression correlated with better responses.

Area of Science:

  • Oncology
  • Immunotherapy
  • Breast Cancer Research

Background:

  • Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its heterogeneity, high recurrence rates, and poor prognosis.
  • Current treatment paradigms for locally advanced unresectable or metastatic TNBC (mTNBC) often involve multiple lines of therapy.

Purpose of the Study:

  • To evaluate the safety and efficacy of first-line treatment combinations involving durvalumab (anti-PD-L1 antibody) in patients with locally advanced unresectable or mTNBC.
  • To assess durvalumab plus paclitaxel, with or without capivasertib (pan-AKT inhibitor) or oleclumab (anti-CD73 antibody).

Main Methods:

  • Phase Ib/II, multiarm, platform study (BEGONIA; NCT03742102) including eligible female participants (≥18 years) with untreated, unresectable, locally advanced/mTNBC.
  • Primary objective: safety and tolerability. Secondary endpoint: objective response rate (ORR).

Main Results:

  • Twenty-three patients received durvalumab plus paclitaxel; 31 received the capivasertib combination; 33 received the oleclumab combination.
  • Grade 3/4 adverse events occurred in 43.5%, 80.6%, and 24.2% of patients, respectively.
  • Confirmed ORRs were 56.5%, 54.8%, and 51.5%, with responses observed across biomarker subgroups.

Conclusions:

  • Durvalumab plus paclitaxel demonstrated clinical activity and tolerability in locally advanced unresectable/mTNBC.
  • Addition of capivasertib or oleclumab did not provide substantial additional benefit.
  • PD-L1 expression was associated with enhanced antitumor activity across all treatment arms.

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