Phase 3 precemtabart tocentecan (CEACAM5 ADC delivering TOP1 inhibitor exatecan) in previously treated mCRC

This randomized, open-label, 3-arm Phase 3 study (PROCEADE-CRC-03) tests whether precemtabart tocentecan (Precem‑TcT; also known as M9140)—a CEACAM5-targeted antibody–drug conjugate that delivers the topoisomerase 1 inhibitor payload exatecan—can improve overall survival versus an active control in previously treated metastatic colorectal cancer. EMD Serono (Merck KGaA, Darmstadt, Germany’s US biopharma business) is evaluating Precem‑TcT as monotherapy and in combination with bevacizumab (Genentech/Roche’s anti‑VEGF monoclonal antibody) against the comparator regimen trifluridine/tipiracil (Taiho Oncology’s oral nucleoside analog + tipiracil thymidine phosphorylase inhibitor) plus bevacizumab. The population is mCRC previously treated with (and progressed on or after) fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab, aligning with a “post-standard backbone” setting where options are limited and survival gains are typically incremental. The scientific/commercial angle is moving a CEACAM5-directed TOP1 ADC into a registrational design, building on Phase 1 signals in mCRC and betting that antigen-targeted delivery plus potential VEGF-synergy can outperform today’s later-line care, which commonly includes trifluridine/tipiracil + bevacizumab (after earlier doublet/triplet chemo ± biologics and immunotherapy for MSI-H).