Japanese-based pharmaceutical company Daiichi Sankyo has begun its Phase I/II trial of U3-1402 to treat patients with HER3-positive metastatic or unresectable breast cancer in Japan.
U3-1402 is a second clinical-stage, investigational antibody drug conjugate comprising a humanised anti-HER3 antibody fused by a peptide linker to a novel topoisomerase I inhibitor (DXd) payload, leveraging on Daiichi Sankyo's payload and linker-payload technologies.
U3-1402 is characterised by a near 8 Drug-Antibody Ratio (DAR), which denotes that nearly eight molecules of DXd are attached per antibody.
The open label Phase I/II trial is divided into three parts, during which the patients will be administered with an intravenous infusion of U3-1402 every three weeks.
Daiichi Sankyo oncology research and development executive vice-president and global head Antoine Yver said: "While treatment for patients with metastatic HER2-negative breast cancer has gradually improved over the past several years, there is still need for improvement, particularly by developing targeted therapies.
"The purpose of this study is to determine whether delivering a cytotoxic agent via a HER3 monoclonal antibody could be an effective and safe approach to treating patients with HER3-overexpressing breast cancer."
The first part of the study will be conducted as a dose escalation study, which will test the safety, tolerability and determine the maximum tolerated dose of U3-1402 in HER3-positive metastatic breast cancer patients who are refractory or intolerant to standard treatment, or who have no available treatment option.
The second part is the dose-finding stage of the study, evaluating the safety and efficacy of U3-1402 and determining the recommended phase II dose in HER3-positive metastatic breast cancer patients who have received six or fewer prior chemotherapy regimens.
The third part of the study will test the safety and efficacy of the recommended dose of U3-1402 in HER3-positive metastatic breast cancer patients who were subjected to six or lesser chemotherapies.