TPS1116 Background: There is a need for effective late-line treatments in metastatic breast cancer. HER3 overexpression in breast cancer is associated with poor prognosis, but there is as yet no approved targeted treatment against HER3. U3-1402 is a novel antibody-drug conjugate (ADC) comprised of a fully humanized anti-HER3 antibody (patritumab) covalently conjugated via a cleavable peptide linker to a derivative of the topoisomerase I inhibitor exatecan. After U3-1402 binds to HER3 on the tumor cell surface, it is internalized and leads to apoptosis via inhibition of topoisomerase I. This ADC achieves a high drug-to-antibody ratio of ~8:1. Methods: This is a Phase 1/2, multicenter, non-randomized, open-label, multiple-dose, first-in-human study in subjects with HER3-positive metastatic breast cancer. The study consists of 3 parts: Dose Escalation, Dose Finding, and Phase 2. In Dose Escalation, safety and tolerability of U3-1402 are evaluated and the maximum tolerated dose is determined using the modified continuous reassessment method with escalation with overdose control. In Dose Finding, the recommended phase 2 dose (RP2D) of U3-1402 is determined using continued assessment of safety and efficacy as well as pharmacokinetic data of U3-1402. Efficacy and safety of the RP2D are further evaluated in Phase 2 part. Patients with locally advanced or metastatic breast cancer who have disease refractory to standard treatment, who cannot tolerate standard treatment, or for whom no standard treatment is available, will be enrolled. Key inclusion criteria include HER3-positive tumor, ECOG performance status 0–1, and measurable disease based on RECIST version 1.1. HER3 expression in tumor tissue will be evaluated with immunohistochemistry at a central laboratory. Prior chemotherapy regimens are restricted to 6 or fewer in Dose Finding and Phase 2, but not in Dose Escalation. Patients will receive U3-1402 intravenously every 3 weeks until unacceptable toxicity or disease progression. Enrollment of an estimated 80 patients is ongoing. Clinical trial information: 02980341.
Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)