Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Ref Type | Journal Article | ||||||||||||
PMID | (31395690) | ||||||||||||
Authors | Koganemaru S, Kuboki Y, Koga Y, Kojima T, Yamauchi M, Maeda N, Kagari T, Hirotani K, Yasunaga M, Matsumura Y, Doi T | ||||||||||||
Title | U3-1402, a Novel HER3-Targeting Antibody-Drug Conjugate, for the Treatment of Colorectal Cancer. | ||||||||||||
|
|||||||||||||
URL | |||||||||||||
Abstract Text | HER3 is overexpressed in several cancers, including colorectal cancer. Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits have not been reported. U3-1402 is a novel HER3-antibody-drug conjugate (ADC) composed of the HER3 antibody patritumab and a novel topoisomerase I inhibitor, DX-8951 derivative (DXd). The sensitivity of DXd was evaluated by a growth inhibition assay. The antitumor activity of U3-1402 was evaluated in a murine xenograft model in which its effects on cells, with a range of HER3 expression levels, were compared with those of patritumab alone, irinotecan, control-ADC, and saline. In the growth inhibition assay, all colorectal cancer cell lines were sensitive to DXd. In the tumor xenograft model, significant tumor regression with U3-1402 was observed both in the DiFi cell line (high HER3 expression; KRAS wild type) and in SW620 (high HER3 expression; KRAS mutation), but no treatment effect was observed in Colo320DM (low HER3 expression). Notably, SW620 tumor growth was significantly suppressed with U3-1402 compared with the saline-treated group (P < 0.001) and showed greater activity compared with the irinotecan group. By contrast, patritumab alone, control-ADC, and saline did not significantly differ in tumor growth inhibition. The antitumor activity of U3-1402 was dependent on HER3 expression level, but not on KRAS mutation status. These results support further investigation of development strategies for U3-1402 in patients with HER3-expressing colorectal cancer. |
Molecular Profile | Treatment Approach |
---|
Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
---|
Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
---|---|---|---|
Patritumab deruxtecan | Patritumab deruxtecan | 15 | 15 |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Patritumab deruxtecan | U3-1402|HER3-DXd|U3 1402|U31402 | HER3 (ERBB3) Antibody 23 | Patritumab deruxtecan (U3-1402) is an antibody-drug conjugate (ADC) comprising an ERBB3 (HER3) antibody and Exatecan, which once internalized may result in apoptotic cell death (PMID: 31395690, PMID: 31661465, PMID: 31471314). |
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 |
---|---|---|---|---|---|---|---|
ERBB3 positive | colorectal cancer | predicted - sensitive | Patritumab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Patritumab treatment resulted in reduced Erbb3 (Her3) phosphorylation in Erbb3 (Her3)-positive colorectal cancer cell lines in culture and modest antitumor activity in cell line xenograft models (PMID: 31395690). | 31395690 |
ERBB3 positive | colorectal cancer | sensitive | Patritumab deruxtecan | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Patritumab Deruxtecan (U3-1402) decreased viability of Erbb3 (Her3)-positive colorectal cancer cell lines in culture and induced significant tumor growth inhibition in cell line xenograft models with intermediate to high Erbb3 (Her3) expression (PMID: 31395690). | 31395690 |