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)

Abstract

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