ESMO Breast 2021 | MIMOSA: monalizumab and trastuzumab in HER2+ breast cancer
Veerle Geurts, MD, Netherlands Cancer Institute, Amsterdam, Netherlands, shares an update on the Phase II MIMOSA trial (NCT04307329) of trastuzumab and monalizumab. Monalizumab is a novel immune checkpoint inhibitor which targets NKG2A receptors which are expressed on tumor infiltrating cytotoxic CD8+ T-cells and NK-cells. This interview took place at the virtual European Society for Medical Oncology (ESMO) Breast Cancer Congress 2021.
Transcript (edited for clarity)
The MIMOSA trial is a new immunotherapy trial for patients with HER2+ metastatic breast cancer. And in the MIMOSA trial, we will treat these patients with a combination of trastuzumab, and the novel immune checkpoint inhibitor, monalizumab.
Targeting the HER2 receptor by trastuzumab-based therapies is now still the cornerstone of treatment for this patient group, but unfortunately, many of these patients eventually become resistant towards trastuzumab-based therapies, so there’s still a need for novel therapeutic strategies for this patient group...
The MIMOSA trial is a new immunotherapy trial for patients with HER2+ metastatic breast cancer. And in the MIMOSA trial, we will treat these patients with a combination of trastuzumab, and the novel immune checkpoint inhibitor, monalizumab.
Targeting the HER2 receptor by trastuzumab-based therapies is now still the cornerstone of treatment for this patient group, but unfortunately, many of these patients eventually become resistant towards trastuzumab-based therapies, so there’s still a need for novel therapeutic strategies for this patient group.
So, the main mechanism for action of trastuzumab is antibody-dependent cellular cytotoxicity, which involves, among others, NK-cells, but the activity of NK-cells and CD8 T-cells is decreased as a result of an interaction between HLA-E expression on tumor cells and the inhibitory receptor NKG2A. And this inhibitory receptor is present on both NK-cells and CD8 T-cells, causing their cytotoxic activity to be decreased.
So, the idea is that monalizumab targets this inhibitory NKG2A receptor, and hopefully this will prevent the interaction between HLA-E on tumor cells, and the inhibitory receptor NKG2A on our immune cells. And we hypothesize that by combining trastuzumab with monalizumab, we will unleash NK-cells and CD8 T-cells, and hopefully can overcome trastuzumab resistance in this patient group.
In the MIMOSA trial, patients with progression after trastuzumab-based treatments will be treated bi-weekly with trastuzumab and monalizumab. Patients will be treated until disease progression or intolerable toxicity, and our primary endpoint of this study is our objective response rates according to RESIST 1.1.
The MIMOSA trial design is a two-stage design, with two cohorts, and in each cohort 11 patients will be included. And these patients will be divided over those two cohorts, based on the amount of tumor-infiltrating lymphocytes in their biopsy.
At baseline and during treatments, at several timepoints we take blood and a biopsy of a metastatic lesion, which will be used for translational research.
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