Immunome, Inc. has registered a first-in-human Phase I clinical trial for 177Lu-IM-3050, a lutetium-177-labeled radioligand targeting fibroblast activation protein-alpha (FAP-α) in patients with FAP-expressing advanced solid tumors. The trial, designated NCT07505771, marks the clinical entry of a radiopharmaceutical program that originated at Purdue University before being commercialized through Morphimmune, Inc. — a university spinout founded by chemist Philip S. Low — and subsequently acquired by Immunome in October 2023. The molecule's arrival in the clinic reflects broader industry momentum behind FAP-directed radioligand therapy as an approach to targeting the tumor stroma across histology-agnostic solid tumor populations.
The IM-3050-101 study is a two-part, open-label, multicenter dose-escalation and expansion trial enrolling approximately 105 adults with relapsed or refractory FAP-positive solid malignancies, confirmed by FAP PET/CT imaging at screening. Part A conducts sequential dose escalation to determine the maximum tolerated dose and recommended expansion dose; Part B evaluates safety and tolerability at the selected dose. Primary endpoints cover treatment-emergent adverse event incidence and recommended dose determination, graded by NCI-CTCAE v5.0 criteria. Secondary endpoints include objective response rate, complete response rate, and disease control rate by RECIST v1.1, alongside radiation dosimetry and pharmacokinetic parameters. The trial is listed as not yet recruiting as of its April 2026 posting, with primary completion expected in December 2029 and full study completion in December 2034.
FAP-α is a type II transmembrane serine protease expressed at low levels in normal adult tissue but upregulated on cancer-associated fibroblasts (CAFs) in a broad range of solid epithelial tumors. Because CAFs constitute the dominant stromal cell population and actively support tumor growth, invasion, and immune evasion, FAP has attracted sustained interest as a theranostic target — one that can be imaged and treated using matched radioligand pairs. First-generation fibroblast activation protein inhibitor (FAPI) compounds demonstrated favorable tumor uptake in PET imaging studies but suffered from rapid clearance that limited their utility as therapeutic vehicles. IM-3050 incorporates an albumin-binding domain intended to extend plasma half-life and increase tumor residence time, an engineering approach documented in a 2024 Journal of Medicinal Chemistry publication on FAP radioligand linker optimization co-authored by researchers with dual Purdue University and Morphimmune affiliations. The therapeutic construct pairs this retained small-molecule FAP ligand with ¹⁷⁷Lu, a beta-emitting radionuclide that delivers DNA-damaging radiation to FAP-expressing stromal cells and, via the crossfire effect, to adjacent tumor cells that may not themselves express FAP. Unlike antibody-drug conjugates, radioligand therapy does not require receptor internalization, which is relevant given FAP's variable internalization kinetics.