Introduction
tumor, DLTs
ADHESION, SOLID TUMORS, TUMOR
Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a transmembrane glycoprotein that is involved in cell adhesion and migration but has limited expression in normal adult tissues (Tusamitamab ravtansine (SAR408701) is an antibody–drug conjugate (ADC) designed to target tumor cells that express CEACAM5 (We previously described the safety, pharmacokinetics, preliminary antitumor activity, and maximum tolerated dose (MTD) of tusamitamab ravtansine in a cohort of patients with advanced solid tumors who received escalating doses in an every 2 weeks (Q2W) schedule in the first-in-human study (NCT02187848; ref. Here, we describe the findings from two cohorts of patients with advanced solid tumors who received alternative dosing schedules of tusamitamab ravtansine in the same phase I clinical study. Escalating loading doses (LDs) at cycle 1, followed by fixed doses Q2W, were assessed to increase the dose/exposure in the first cycle to potentially improve efficacy while limiting the incidence of DLTs that were observed at or above the MTD in the Q2W dose-escalation part of the first-in-human study. Administration every 3 weeks (Q3W) was also assessed to align with the schedule of standard-of-care treatments at the time of the study.