Phase 1 CEA-PRIT 2.0 pretargeted alpha therapy targeting CEACAM5 (CEA)

This first-in-human, open-label Phase 1 study from Roche/Genentech evaluates CEA-PRIT 2.0, a multi-step “pretargeted” radioimmunotherapy designed to deliver the alpha-emitter lead-212 to CEACAM5 (CEA)–expressing metastatic colorectal cancer while limiting normal-tissue radiation. The intervention uses SeParated v-domains LInkage Technology antibodies (SPLIT Abs) to bind tumor CEA (CEACAM5), then administers a radiolabeled small-molecule payload (212Pb‑DOTAM) that localizes to the pretargeted antibody; an imaging dosimetry step with 203Pb‑DOTAM is used in Part 1 to estimate radiation distribution before therapeutic dosing. Parts 2–3 escalate 212Pb‑DOTAM administered activity to define maximum tolerated activity/recommended Phase 2 activity, then expand at that level. Eligible patients have metastatic microsatellite-stable/proficient MMR CRC after intolerance or progression on available standard therapies; today’s care after standard fluoropyrimidine/oxaliplatin/irinotecan regimens is typically later-line biologics (VEGF- and EGFR-targeted agents when RAS wild-type) and oral options like regorafenib or trifluridine/tipiracil, with limited benefit—making targeted alpha delivery an interesting modality bet in a hard-to-treat population.