75TiP Open-label, phase II study of tusamitamab ravtansine (SAR408701) in combination with pembrolizumab and with pembrolizumab + platinum-based chemotherapy +/− pemetrexed in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05)

Pembrolizumab +/− chemotherapy (CT) is the current, standard first-line (1L) treatment for advanced/metastatic nonsquamous (NSQ) non-small cell lung cancer (NSCLC) with no EGFR/ALK alterations. Carcinoembryonic antigen-related adhesion molecule 5 (CEACAM5) surface expressed on some tumors, including NSCLC. Tusamitamab ravtansine (tusa), an anti-CEACAM5 mAb conjugated potent cytotoxic maytansinoid antitubulin agent DM4, has shown encouraging single-agent results in patients (pts) heavily pretreated CEACAM5+ NSQ NSCLC; a phase 3 monotherapy study ongoing pts prior CT and immune checkpoint inhibitors. Combinations of tusa pembrolizumab may improve 1L outcomes without additional toxicity. CARMEN-LC05 aims to assess, NSCLC, safety antitumor activity combination (Part A); + platinum-based B); pemetrexed C). Pts NSCLC high CEACAM5 expression (immunohistochemistry intensity ≥2+ ≥50% tumor cells) are assigned Part A, B, or C based investigator’s choice; moderate expressors (≥2+ 1% <50%) C. ≥18 years old EGFR, BRAF, ALK/ROS aberrations; disease; biopsy amenable ECOG PS 0–1. Key exclusion criteria unresolved corneal disorders; concurrent anticancer immunosuppressive therapies; past therapy targeting CEACAM5, PD-L1, CD137, CTLA-4; maytansinoids. A run-in Parts will assess dose-limiting toxicities each part determine recommended dose when combined other therapies. The primary objective tolerability combinations secondary objectives safety/tolerability, (objective response rate), pharmacokinetics, immunogenicity. As Jan 5, 2022, 27 sites 7 countries recruiting. NCT04524689. Medical writing assistance was provided by Chase Pectol, PhD, Elizabeth Strickland, inScience Communications, Springer Healthcare (Philadelphia, PA). Sanofi, Inc.