drugsAgentPhase 1

Actinium-225 FPI-2068

aka 225Ac-FPI-2068, [225Ac]-FPI-2068

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.

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.

Schematic of the modality · alpha therapy · not a molecule; see the Targeted alpha therapy page

See it in action

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.

1. What happens next: the radiopharmaceutical schematic

How it works, step by step · animated schematic, not to scale

Targeted alpha therapy →

2. Step by step

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1.Actinium-225 FPI-2068 binds its target on the cancer cell or is taken up by it.

Modality

alpha therapy

Mechanism

Brand / code

FPI-2068

Trials

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Actinium-225 FPI-2068

intervention: Actinium-225 FPI-2068

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