Phase 1a/b study of LY4257496, a GRPR-targeted beta emitter radioligand

This two-part, open-label trial evaluates safety, tolerability, and preliminary efficacy of LY4257496 administered alone or with standard-of-care agents—including fulvestrant, imlunestrant, aromatase inhibitor, capecitabine, and abemaciclib—in adults with GRPR-positive advanced breast, colorectal, prostate, and endometrial cancers. Sponsored by Eli Lilly and Company, the study focuses on dosing optimization and combination regimens. Radioligand therapy is established in PSMA-positive prostate and SSTR-positive NETs, but there’s no GRPR-directed SoC; this explores a new target and combination pairings to broaden RLT reach.