{"entity":{"id":"ac-225-fpi-2068","kind":"drug","name":"Actinium-225 FPI-2068","aka":["225Ac-FPI-2068","[225Ac]-FPI-2068"],"tldr":"An antibody engineered to grab onto two markers found together on some solid tumours, but not on healthy cells, carries a powerful short-range radioactive payload into the tumour to try to destroy it.","summary":"225Ac-FPI-2068 is a bispecific targeted alpha therapy (TAT) from Fusion Pharmaceuticals, developed jointly with AstraZeneca, designed for solid tumours that co-express EGFR and cMET (including head and neck squamous cell carcinoma, non-small cell lung cancer, colorectal cancer and pancreatic ductal adenocarcinoma). It combines the bispecific antibody FPI-2053 with the alpha emitter actinium-225 via a DOTA chelate; an indium-111-labelled version of the same antibody (FPI-2107) is used as a companion imaging and dosimetry tracer, and unlabelled FPI-2053 is given as a pre-dose to optimise biodistribution.\n\nPreclinical data presented at AACR-NCI-EORTC in 2023 showed FPI-2068 bound EGFR/cMET-expressing colorectal and lung cancer cell lines, internalised into tumour cells, and caused prolonged tumour regression (over 28 days) in xenograft models at doses of 370-740 kBq/kg, with evidence of DNA double-strand break formation and apoptosis consistent with its proposed mechanism. The FDA cleared investigational new drug (IND) applications for FPI-2068 and FPI-2107 in April 2023.\n\nA first-in-human phase 1, two-part, dose-escalation trial (ClinicalTrials.gov NCT06147037) opened in July 2024 across US and Canadian sites, evaluating safety, tolerability, dosimetry, biodistribution and pharmacokinetics in adults with advanced EGFR/cMET-co-expressing solid tumours; Part A optimises the FPI-2053 pre-dose and Part B escalates the actinium-225 dose. As of the most recent public update (October 2025), no human efficacy or safety results had been reported; the study's estimated primary completion is December 2026/2027.","status":"phase-1","asOf":"2026-09-22","links":[{"label":"Fusion Pharmaceuticals: AACR-NCI-EORTC 2023 preclinical poster on FPI-2068","url":"https://fusionpharma.com/wp-content/uploads/2023/10/2068_AACR-poster_2023_Final.pdf"},{"label":"Fusion Pharmaceuticals: IND clearance for FPI-2068 and FPI-2107, April 2023","url":"https://www.pharmaceutical-technology.com/news/fusion-fda-ind-fpi-2068/"},{"label":"ClinicalTrials.gov: NCT06147037","url":"https://clinicaltrials.gov/study/NCT06147037"}],"tags":["alpha therapy","bispecific antibody","EGFR","cMET","actinium-225","phase 1"],"related":["fpi-2265","in-111","ac-225"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":["fusion-pharma","astrazeneca"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["EGFR and cMET are not yet represented as target records in this graph, so no targets[] link is made here; add them once those target records exist."],"code":"FPI-2068","modality":"alpha therapy","mechanism":"A bispecific, humanised IgG antibody (FPI-2053) that binds both EGFR and cMET, conjugated via a DOTA chelator to the alpha-emitting radioisotope actinium-225. Because it targets two receptors that are co-expressed on tumour cells but not usually together on normal tissue, the antibody is designed to internalise preferentially into tumour cells, delivering alpha particles that cause DNA double-strand breaks.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/ac-225-fpi-2068/","neighbours":{"drug":[{"id":"fpi-2265","kind":"drug","name":"FPI-2265","route":"/drugs/fpi-2265/"}],"isotope":[{"id":"ac-225","kind":"isotope","name":"Actinium-225","route":"/isotopes/ac-225/"},{"id":"in-111","kind":"isotope","name":"Indium-111","route":"/isotopes/in-111/"}],"technology":[{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"company":[{"id":"astrazeneca","kind":"company","name":"AstraZeneca","route":"/companies/astrazeneca/"},{"id":"fusion-pharma","kind":"company","name":"Fusion Pharmaceuticals (AstraZeneca)","route":"/companies/fusion-pharma/"}]}}