# FAP-targeted radioligand therapy for sarcoma

Source: https://nuclide.cc/ideas/idea-fap-theranostics-sarcoma/  
Nuclide record `idea-fap-theranostics-sarcoma` (Idea). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Sarcomas, a group of rare and hard-to-treat cancers, often carry a marker called FAP not just on the supporting tissue around the tumour but on the cancer cells themselves. A radioactive drug built to find FAP is being tried as a treatment, but the small studies done so far disagree about whether it actually shrinks tumours.

## Summary

Fibroblast activation protein (FAP) is usually found on the stromal cells surrounding a tumour rather than on cancer cells directly, which limits how selective a FAP-targeted therapy can be, but sarcomas are one of the few cancer types where the tumour cells themselves can express FAP. 68Ga-FAPI PET has shown superior lesion detection compared with 18F-FDG PET across multiple sarcoma subtypes in prospective imaging cohorts, making FAP an attractive target for a therapeutic radioligand in a disease with essentially no PSMA or somatostatin-receptor expression to exploit.

The handful of early-phase therapeutic studies published so far give a mixed signal. A 5-patient pilot study of 177Lu-FAPI-2286 in metastatic sarcoma reported partial response in 4 of 5 patients by RECIST, with a 52% mean reduction in primary tumour volume. A separate, later 6-patient exploratory study of the same drug in metastatic sarcoma found no RECIST partial or complete responses at all, only stable disease in some patients (with mixed results by other volumetric metrics), a median overall survival of just 4 months, and 3 of 6 patients dying during follow-up. A first-in-human dose-escalation trial of a related FAP ligand, 177Lu-FAPI-XT (NCT06211647/NCT06197139, 14 patients across several tumour types including fibroblastic sarcoma subtypes), found an overall disease control rate of 35.7%, rising to 50% in the sarcoma subtypes specifically, but no complete or partial responses in the whole cohort, alongside a favourable safety profile with no dose-limiting toxicity up to 11.1 GBq. Separately, the Novartis-sponsored LuMIERE trial (NCT04939610) is testing 177Lu-FAP-2286 in pancreatic, non-small-cell lung and breast cancer, not specifically in sarcoma.

These are all small, uncontrolled, single-arm case series (5-14 patients each) with conflicting response rates, so whether FAP-targeted radioligand therapy has genuine, reproducible activity in sarcoma, and if so in which histological subtypes, remains unresolved.

## Fields

- Kind: Idea
- Last checked: 2026-09-22
- Tags: FAP; sarcoma; theranostics
- Hypothesis: Because sarcoma tumour cells, unlike most other cancers, can themselves express fibroblast activation protein, targeting FAP with a therapeutic radioligand will produce meaningful and reproducible disease control in advanced sarcoma, a cancer type with almost no PSMA or somatostatin-receptor expression to exploit with existing radioligand therapies.
- Rationale: 68Ga-FAPI PET reliably detects more sarcoma lesions than 18F-FDG PET, establishing that FAP is a genuine, targetable marker in this disease. However, the three published or presented therapeutic case series (5, 6 and 14 patients respectively) give conflicting results: one reported 4/5 partial responses, another reported zero objective responses with a 4-month median overall survival in a similar 6-patient cohort, and a third reported disease control (mostly stable disease) in half of its sarcoma subtype patients but no objective responses at all. This inconsistency across small, uncontrolled series means the true response rate and the subtypes most likely to benefit (solitary fibrous tumour and myofibroblastic sarcoma showed the most disease control in the dose-escalation study) are not yet established.
- Proposed test: A larger, prospective phase 2 basket trial of a FAP-targeted radioligand (such as 177Lu-FAPI-2286 or 177Lu-FAPI-XT) restricted to FAP-PET-selected sarcoma patients, ideally enriched for the subtypes (solitary fibrous tumour, myofibroblastic sarcoma) that showed the most disease control in the dose-escalation series, roughly 40-60 patients, with RECIST objective response rate and progression-free survival as endpoints, to resolve the conflicting signal from the existing small case series.
- Maturity: early-clinical
- Actor: research

## Sources

- Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma (EJNMMI, 2024): https://pubmed.ncbi.nlm.nih.gov/39060377/
- Safety and efficacy of 177Lu-FAPI-XT radioligand therapy in advanced sarcoma and other cancer entities: first-in-human, dose-escalation study (EJNMMI, 2026): https://pubmed.ncbi.nlm.nih.gov/41087606/
- Theranostics in Sarcoma: A Critical Review of Current Evidence and Future Directions (2026 review): https://link.springer.com/content/pdf/10.1007/s11864-026-01386-0.pdf
- A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE) (ClinicalTrials.gov, NCT04939610): https://clinicaltrials.gov/study/NCT04939610

## Connected records

- targets: [FAP](https://nuclide.cc/targets/fap/)
- drugs: [FAP-2286 (177Lu / 68Ga)](https://nuclide.cc/drugs/fap-2286/)
- technologies: [FAPI PET](https://nuclide.cc/technologies/fapi-pet/)
- ideas: [FAP theranostics as a pan-cancer stromal strategy](https://nuclide.cc/ideas/idea-fap-theranostics-pancancer/)
- isotopes: [Fluorine-18](https://nuclide.cc/isotopes/f-18/), [Gallium-68](https://nuclide.cc/isotopes/ga-68/), [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)

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