Phase 3 petosemtamab (EGFR×LGR5 bispecific antibody) vs cetuximab in 1L left-sided mCRC

Genmab’s LiGeR-CRC1 is a randomized, open-label Phase 3 trial testing whether petosemtamab (MCLA-158; an EGFR×LGR5-directed bispecific monoclonal antibody designed to block EGFR signaling and target LGR5-expressing tumor-initiating cells) improves outcomes when combined with investigator’s choice chemotherapy. Participants with unresectable or metastatic, left-sided colorectal adenocarcinoma that is RAS and BRAF wild-type receive petosemtamab plus mFOLFOX6 (5-FU/leucovorin/oxaliplatin; cytotoxic DNA-damage/antimetabolite backbone) or FOLFIRI (5-FU/leucovorin/irinotecan; topoisomerase I inhibition) versus the standard anti-EGFR comparator, cetuximab (EGFR monoclonal antibody; Eli Lilly/BMS heritage) plus the same chemo choice. The key angle is a next-generation “beyond EGFR” biologic in a segment where anti-EGFR + doublet chemotherapy is already a core first-line option for left-sided, RAS/RAF wild-type metastatic disease; today’s care is typically FOLFOX or FOLFIRI plus an EGFR antibody (cetuximab or panitumumab) or bevacizumab depending on goals and molecular context, with later-line options including additional targeted agents and antibody–drug conjugates where appropriate. This trial essentially asks whether adding LGR5 biology to EGFR blockade can outcompete a well-established EGFR mAb standard without placebo.