EP08.02-030 Tusamitamab Ravtansine in Patients with NSQ NSCLC and Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), one member of the carcinoembryonic antigen (CEA) family, is a cell-surface glycoprotein that is highly expressed on epithelial tumor cells. Circulating CEA is the shed form of membranous CEA family proteins. Tusamitamab ravtansine (SAR408701) is an anti-CEACAM5 antibody conjugated to the cytotoxic maytansinoid agent DM4. Tusamitamab ravtansine 100 mg/m2 every other week (Q2W) showed encouraging antitumor activity in the first-in-human study (NCT02187848) in a cohort of 64 heavily pretreated patients with nonsquamous non-small cell lung cancer (NSQ NSCLC) and high CEACAM5 expression (defined as ≥ 2+ intensity in ≥ 50% of the tumor cells) as determined by immunohistochemistry (IHC) methods, but fewer responses in a cohort of patients (n = 28) with moderate CEACAM5 expression (defined as ≥ 2+ intensity in ≥ 1% to < 50% of the tumor cells) (Gazzah A et al. J Clin Oncol. 2020;38[15 suppl]:9505). A Phase 3 study (NCT04154956) is currently ongoing in previously treated patients with NSQ NSCLC and high CEACAM5 expression comparing tusamitamab ravtansine to docetaxel. CARMEN-LC06 (NCT05245071) aims to evaluate whether patients with a high circulating CEA level at baseline benefit from tusamitamab ravtansine treatment despite negative or moderate CEACAM5 expression in archival biopsy sample.