Breast (Aug 2023)

Unleashing NK- and CD8 T cells by combining monalizumab and trastuzumab for metastatic HER2-positive breast cancer: Results of the MIMOSA trial

  • V.C.M. Geurts,
  • L. Voorwerk,
  • S. Balduzzi,
  • R. Salgado,
  • K. Van de Vijver,
  • M.G.J. van Dongen,
  • I. Kemper,
  • I.A.M. Mandjes,
  • M. Heuver,
  • W. Sparreboom,
  • J.B.A.G. Haanen,
  • G.S. Sonke,
  • H.M. Horlings,
  • M. Kok

Journal volume & issue
Vol. 70
pp. 76 – 81

Abstract

Read online

The large majority of patients with HER2-positive metastatic breast cancer (MBC) will eventually develop resistance to anti-HER2 therapy and die of this disease. Despite, relatively high levels of stromal tumor infiltrating lymphocytes (sTILs), PD1-blockade has only shown modest responses. Monalizumab targets the inhibitory immune checkpoint NKG2A, thereby unleashing NK- and CD8 T cells. We hypothesized that monalizumab synergizes with trastuzumab by promoting antibody-dependent cell-mediated cytotoxicity.In the phase II MIMOSA-trial, HER2-positive MBC patients were treated with trastuzumab and 750 mg monalizumab every two weeks. Following a Simon's two-stage design, 11 patients were included in stage I of the trial.Treatment was well tolerated with no dose-limiting toxicities. No objective responses were observed. Therefore, the MIMOSA-trial did not meet its primary endpoint.In summary, despite the strong preclinical rationale, the novel combination of monalizumab and trastuzumab does not induce objective responses in heavily pre-treated HER2-positive MBC patients.

Keywords