Unleashing NK- and CD8 T cells by combining monalizumab and trastuzumab for metastatic HER2-positive breast cancer: Results of the MIMOSA trial
The Breast(2023)
摘要
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 infil-trating lymphocytes (sTILs), PD1-blockade has only shown modest responses. Monalizumab targets the inhibi-tory 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. There-fore, 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.
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关键词
Breast cancer,Immunotherapy,Checkpoint blockade
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