Targeting Fibroblast Activation Protein with [177Lu]Lu-FAP-2286 in Patients with Advanced Solid Tumors in the Phase I LuMIERE Trial

Jonathan McConathy; Vadim S Koshkin; Yusuf Menda; Jordi Rodon; Ajit H Goenka; Ryan H Moy; Sophie Morse; Arnaud Demange; Lars Blumenstein; Burcu Babaoglan; Paola Aimone; Thomas A Hope

doi:10.1158/1078-0432.CCR-25-4356

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Targeting Fibroblast Activation Protein with [177Lu]Lu-FAP-2286 in Patients with Advanced Solid Tumors in the Phase I LuMIERE Trial

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Targeting Fibroblast Activation Protein with [177Lu]Lu-FAP-2286 in Patients with Advanced Solid Tumors in the Phase I LuMIERE Trial

Jonathan McConathy, Vadim S Koshkin, Yusuf Menda, Jordi Rodon, Ajit H Goenka, Ryan H Moy, Sophie Morse, Arnaud Demange, Lars Blumenstein, Burcu Babaoglan, …

Clinical cancer research

06/01/2026

DOI: 10.1158/1078-0432.CCR-25-4356

PMID: 42223513

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Abstract

Fibroblast activation protein (FAP) is an attractive target for radiopharmaceutical therapy. Phase I of the LuMIERE study (ClinicalTrials.gov, NCT04939610) investigated the safety of [177Lu]Lu-FAP-2286 (177Lu-FAP-2286) in heavily pretreated patients with advanced solid tumors and identified the recommended phase II dosage (RP2D). LuMIERE is a prospective, open-label, non-randomized, phase I/II, multicenter study. Phase I followed a Bayesian optimal interval design evaluating four escalating activity levels of 177Lu-FAP-2286 (3.70, 5.55, 7.40, and 9.25 GBq). Patients were selected by positive [68Ga]Ga-FAP-2286 (68Ga-FAP-2286, also known as [68Ga]Ga-HKG301) PET/CT imaging on all target lesions (SUVmax ≥1.5× SUVmean of mediastinal blood pool). 177Lu-FAP-2286 was administered intravenously every 6 weeks for ≤6 cycles. The primary endpoint was dosage-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs). Of 35 patients imaged with 68Ga-FAP-2286, 27 received 177Lu-FAP-2286 (3.70 GBq, n=3; 5.55 GBq, n=6; 7.40 GBq, n=7; 9.25 GBq, n=11). Two DLTs were observed: one patient who received 5.55 GBq of 177Lu-FAP-2286 experienced Grade 4 lymphopenia and one patient who received 9.25 GBq experienced Grade 3 hemoptysis; these were the only treatment-related Grade ≥3 TEAEs. All-cause Grade ≥3 TEAEs were reported for 11 patients (40.7%). The RP2D for 177Lu-FAP-2286 monotherapy was determined as 9.25 GBq. Preliminary RECIST efficacy findings demonstrated partial response in one patient and stable disease in 10 patients (maintained for at least two assessments in six patients). 177Lu-FAP-2286 was well tolerated in patients with advanced solid tumors. The safety and preliminary efficacy findings support its continued development in phase II.

Details

Title: Subtitle: Targeting Fibroblast Activation Protein with [177Lu]Lu-FAP-2286 in Patients with Advanced Solid Tumors in the Phase I LuMIERE Trial
Creators: Jonathan McConathy - University of Alabama at Birmingham
Vadim S Koshkin - University of California, San Francisco
Yusuf Menda - University of Iowa Hospitals and Clinics
Jordi Rodon - The University of Texas MD Anderson Cancer Center
Ajit H Goenka - Mayo Clinic
Ryan H Moy - Columbia University Irving Medical Center
Sophie Morse - Novartis (Switzerland)
Arnaud Demange - Advanced Applications (United States)
Lars Blumenstein - Novartis (Switzerland)
Burcu Babaoglan - Novartis (United Kingdom)
Paola Aimone - Novartis Foundation
Thomas A Hope - University of California, San Francisco
Resource Type: Journal article
Publication Details: Clinical cancer research
DOI: 10.1158/1078-0432.CCR-25-4356
PMID: 42223513
eISSN: 1557-3265
Language: English
Electronic publication date: 06/01/2026
Academic Unit: Radiology; Radiation Oncology
Record Identifier: 9985167575502771

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