71P Biomarker analysis from phase I/II study of tusamitamab ravtansine (SAR408701) in patients with advanced non-small cell lung cancer (NSCLC)

Tusamitamab ravtansine is an antibody-drug conjugate of a humanized carcinoembryonic antigen (CEA)-related cell adhesion molecule 5 (CEACAM5)-specific monoclonal antibody linked to DM4. A phase I/II study showed tusamitamab antitumor activity in pretreated patients (pts) with advanced nonsquamous NSCLC and high CEACAM5 expression. Here, we explore biomarker associations tumor expression by immunohistochemistry (IHC), whether biomarkers predict objective response rate (ORR). We assessed IHC, RNA sequencing, whole exome sequencing (WES) on latest archival samples; circulating (cCEACAM5) CEA (cCEA). enrolled 2 cohorts pts IHC membrane at ≥2+ intensity: ≥50% cells (high expressors, HEs, n = 64); ≥1% <50% (moderate MEs, 28). Pts received 100 mg/m2 IV every weeks. cCEA cCEACAM5 were strongly associated (Spearman rho, 0.9), weak between or 0.3 0.4, respectively). Higher levels mRNA observed HEs vs MEs (P 0.0027). EGFR KRAS genetic alterations WES present 44.8% 65.5% respectively, 21.4% 78.6% respectively. Confirmed partial responses seen 13/64 (ORR 20.3%) 2/28 7.1%). In available baseline (BL) data, 25/62 (40.3%) had level ≥100 μg/L, median value 71.6 μg/L (range 1–8809); corresponding values 7/28 (25.0%) 12.4 0.5–684). evaluable BL data (n 61), ORR was 10/24 (41.7%) (≥100 μg/L) 3/37 (8.1%) lowcCEA (<100 μg/L); ORRs 0/7 2/21 (9.5%). Conclusions: numerically greater low (41.7% 8.1%). Associations also between: cCEACAM5; CEACAM5, cCEA, levels, but not actionable oncogenic drivers. NCT02187848. Medical writing provided Michael Stillman Julian Martins, inScience Communications funded Sanofi.