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
Affiliations
V.C.M. Geurts
Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
L. Voorwerk
Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
S. Balduzzi
Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands
R. Salgado
Department of Pathology, ZAS, Antwerp, Belgium; Division of Research, Peter Mac Callum Cancer Center, Melbourne, Victoria, Australia
K. Van de Vijver
Department of Pathology, University Hospital Ghent, Cancer Research Institute Ghent (CRIG), Ghent, Belgium
M.G.J. van Dongen
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
I. Kemper
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
I.A.M. Mandjes
Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands
M. Heuver
Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands
W. Sparreboom
Astra Zeneca, The Hague, the Netherlands
J.B.A.G. Haanen
Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
G.S. Sonke
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
H.M. Horlings
Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
M. Kok
Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Corresponding author. Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
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.
