PURPOSE:DLYE5953A is an antibody-drug conjugate consisting of an anti-LY6E antibody covalently linked to the cytotoxic agent monomethyl auristatin E. This study characterized the safety, pharmacokinetics, immunogenicity, potential biomarkers, and anti-tumor activity of DLYE5953A in patients with metastatic solid tumors.
EXPERIMENTAL DESIGN:This was a phase I, open-label, 3+3 dose-escalation, and dose expansion study of DLYE5953A administered intravenously every 21 days (Q3W) in patients with locally advanced or metastatic solid malignancies.
RESULTS:Sixty-eight patients received DLYE5953A (median: 4 cycles; range: 1-27). No dose limiting toxicities were identified during dose escalation (0.2-2.4 mg/kg; n=20). The recommended phase II dose (RP2D) of 2.4 mg/kg Q3W was based on overall safety and tolerability. Dose expansion cohorts for HER2-negative metastatic breast cancer (HER2-negative MBC) (n=23) and non-small cell lung cancer (NSCLC) (n=25) patients were enrolled at the RP2D. Among patients receiving DLYE5953A 2.4 mg/kg (n=55), the most common (>=30%) related adverse events (AEs) included alopecia, fatigue, nausea, and peripheral neuropathy. Grade >=3 related AEs occurred in 14/55 (26%) of patients, with neutropenia being the most common (13%). DLYE5953A demonstrated linear total antibody pharmacokinetics at doses of >=0.8 mg/kg with low unconjugated MMAE levels in blood. Partial response was confirmed in 8/68 (12%) patients, including 3/29 MBC (10%) and 5/25 NSCLC (20%) patients at the RP2D. Stable disease was the best response for 37/68 (54%) patients.
CONCLUSIONS:DLYE5953A administered at 2.4 mg/kg has acceptable safety. Preliminary evidence of anti-tumor activity in HER2-negative MBC and NSCLC patients supports further investigation of LY6E as a therapeutic target.