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Ref Type Journal Article
PMID (31292166)
Authors Le Joncour V, Martins A, Puhka M, Isola J, Salmikangas M, Laakkonen P, Joensuu H, Barok M
Title A Novel Anti-HER2 Antibody-Drug Conjugate XMT-1522 for HER2-Positive Breast and Gastric Cancers Resistant to Trastuzumab Emtansine.
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Abstract Text Most patients with HER2-positive breast or gastric cancer exhibit primary or acquired resistance to trastuzumab emtansine (T-DM1), and such patients may have limited therapeutic options. XMT-1522 is a novel anti-HER2 antibody-drug conjugate. We compared XMT-1522 to T-DM1 in preclinical models. The effects of XMT-1522 and T-DM1 on cell survival and apoptosis were compared in six HER2-positive breast cancer or gastric cancer cell lines, of which three lines were T-DM1-sensitive (N-87, OE-19, JIMT-1) and three T-DM1-resistant (RN-87, ROE-19, SNU-216). We compared these agents also in the HER2-negative breast cancer cell line MCF-7, and in mouse RN-87 and JIMT-1 xenograft models. Cell survival was assessed using the AlamarBlue method and apoptosis with the Caspase-Glo 3/7 method. XMT-1522 inhibited the growth of all six HER2-positive cell lines. The proportions of cells that survived XMT-1522 treatment were smaller as compared with T-DM1, particularly in the T-DM1-resistant cell lines. XMT-1522 induced more cell apoptosis compared with T-DM1. While RN-87 and JIMT-1 xenograft tumors progressed on T-DM1 treatment, all tumors responded to XMT-1522, and all but one tumor disappeared during the XMT-1522 treatment. XMT-1522 had a strong antitumor effect on RN-87 and JIMT-1 xenografts that progressed on T-DM1. We conclude that XMT-1522 was effective in HER2-positive breast cancer and gastric cancer cell lines resistant to T-DM1, and in xenograft models resistant to T-DM1. The results support the testing of XMT-1522 in clinical trials in patients with HER2-positive cancer.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
XMT-1522 XMT-1522 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
XMT-1522 XMT1522|XMT 1522 HER2 (ERBB2) Antibody 72 HER2 (ERBB2) Antibody-Drug Conjugate 27 XMT-1522 is an antibody-drug conjugate (ADC) comprising an ERBB2 (HER2)-targeted antibody linked to auristatin, which delivers the cytotoxic agent to Erbb2 (Her2)-expressing tumor cells, potentially resulting in decreased tumor growth (PMID: 31292166).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References