# Actinium-225 FPI-2068

Source: https://nuclide.cc/drugs/ac-225-fpi-2068/  
Nuclide record `ac-225-fpi-2068` (Agent). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

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.

Preclinical 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.

A 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.

## Fields

- Kind: Agent
- Status: phase-1
- Last checked: 2026-09-22
- Also known as: 225Ac-FPI-2068; [225Ac]-FPI-2068
- Tags: alpha therapy; bispecific antibody; EGFR; cMET; actinium-225; phase 1
- 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.

## 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.

## Sources

- Fusion Pharmaceuticals: AACR-NCI-EORTC 2023 preclinical poster on FPI-2068: https://fusionpharma.com/wp-content/uploads/2023/10/2068_AACR-poster_2023_Final.pdf
- Fusion Pharmaceuticals: IND clearance for FPI-2068 and FPI-2107, April 2023: https://www.pharmaceutical-technology.com/news/fusion-fda-ind-fpi-2068/
- ClinicalTrials.gov: NCT06147037: https://clinicaltrials.gov/study/NCT06147037

## Connected records

- drugs: [FPI-2265](https://nuclide.cc/drugs/fpi-2265/)
- isotopes: [Actinium-225](https://nuclide.cc/isotopes/ac-225/), [Indium-111](https://nuclide.cc/isotopes/in-111/)
- technologies: [Targeted alpha therapy](https://nuclide.cc/technologies/targeted-alpha-therapy/)
- companies: [AstraZeneca](https://nuclide.cc/companies/astrazeneca/), [Fusion Pharmaceuticals (AstraZeneca)](https://nuclide.cc/companies/fusion-pharma/)

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