A Phase I Study of SAR566658, an Anti CA6-antibody Drug Conjugate (ADC), in Patients (pts) with CA6-positive Advanced Solid Tumors (Sts)(nct01156870).

2511Background: SAR566658 (SAR) is a maytansinoid-loaded ADC targeting CA6, a sialoglycotope of MUC-1 over-expressed in solid tumors and rarely in normal tissues. Methods: Phase I dose escalation and expansion study to evaluate SAR intravenous administration as single agent every 3 weeks (q3w) and 2 weeks (q2w). Primary objective included dose limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended dose (RD). Secondary objectives were PK, PD and preliminary efficacy assessment (RECIST1.1). Results: One hundred and fourteen patients (Pts) with heavily pretreated solid tumors expressing CA6 in ≥ 30% tumor cells with an intensity 2/3+ by immunohistochemistry were enrolled. SAR was administered across 11 dose levels (DLs) (10 to 240 mg/m² q3w and 120 mg/m² q2w). DLTs [1 grade (Gr) 3 diarrhea and 2 Gr3 keratitis] were observed at 240 mg/m². Initial RD was 190 mg/m² however a high incidence of keratopathy was seen mainly at cycle 2. PK/safety simulation, preserving drug exposure and limiting ke...