Unleashing NK- and CD8 T cells by combining monalizumab and trastuzumab for metastatic HER2-positive breast cancer: Results of the MIMOSA trial
- Author(s)
- Geurts, VCM; Voorwerk, L; Balduzzi, S; Salgado, R; Van de Vijver, K; van Dongen, MGJ; Kemper, I; Mandjes, IAM; Heuver, M; Sparreboom, W; Haanen, Jbag; Sonke, GS; Horlings, HM; Kok, M;
- Journal Title
- Breast
- Publication Type
- Research article
- Abstract
- 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
- Female; Humans; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *Breast Neoplasms/pathology; CD8-Positive T-Lymphocytes/pathology; *Mimosa; Receptor, ErbB-2; Trastuzumab/therapeutic use; Breast cancer; Checkpoint blockade; Immunotherapy
- Department(s)
- Laboratory Research
- PubMed ID
- 37393645
- Publisher's Version
- https://doi.org/10.1016/j.breast.2023.06.007
- Open Access at Publisher's Site
https://doi.org/10.1016/j.breast.2023.06.007- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-20 06:08:16
Last Modified: 2024-08-20 06:56:56