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

Autor: Geurts VCM; Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Voorwerk L; Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Balduzzi S; Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands., Salgado R; Department of Pathology, ZAS, Antwerp, Belgium; Division of Research, Peter Mac Callum Cancer Center, Melbourne, Victoria, Australia., Van de Vijver K; Department of Pathology, University Hospital Ghent, Cancer Research Institute Ghent (CRIG), Ghent, Belgium., van Dongen MGJ; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Kemper I; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Mandjes IAM; Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands., Heuver M; Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands., Sparreboom W; Astra Zeneca, The Hague, the Netherlands., Haanen JBAG; Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Sonke GS; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Horlings HM; Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Kok M; Division of Tumor Biology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands. Electronic address: M.Kok@nki.nl.
Jazyk: angličtina
Zdroj: Breast (Edinburgh, Scotland) [Breast] 2023 Aug; Vol. 70, pp. 76-81. Date of Electronic Publication: 2023 Jun 27.
DOI: 10.1016/j.breast.2023.06.007
Abstrakt: 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.
Competing Interests: Declaration of competing interest VCM Geurts, L Voorwerk, S Balduzzi, I Kemper, IAM Mandjes, M Heuver-Mes: no disclosures. MGJ van Dongen: advisory role for Relay Therapeutics. R Salgado: Research support from: Merck, Puma Biotechnology and Roche. Non-financial support from Merck and BMS. Advisory roles for: BMS, Exact Sciences and Roche outside the submitted work. K van de Vijver: Advisory roles for/consultancy fee paid to the institute: AstraZeneca, Exact Sciences, GSK, outside the submitted work. W Sparreboom: employment: AstraZeneca. JBAG Haanen: advisory roles for Achilles Tx, BioNTech, BMS, GSK, Iovance Bio, Instil Bio, Ipsen, MSD, Molecular Partners, Novartis, Neogene Tx, Pfizer, Roche, Sanofie, Scenic, T-Knife. Received grant support from Amgen, BioNTech, BMS, MSD, Novartis and has stock options in Neogene Tx. GS Sonke: Received funding paid to the institute from: Agendia, AstraZeneca, Merck, Novartis and Roche. Advisory roles for: Biovica, Seagen outside the submitted work. HM Horlings: consultancy fee paid to institute: Roche, and is advisor for SlideScore and Ellogon, outside the submitted work. M Kok: Received funding paid to the institute from BMS, Roche, AstraZeneca. Advisory roles for: Daiichi Sankyo, BMS, MSD, Roche outside the submitted work. Speakers’ fee from: Roche, BMS and Gilead.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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