Skip to content
DraconiticResearch
Search Sources API
190,332 studies31 sourcesUpdated 15 min ago
Peer-reviewedCC BYClinical Cancer Research

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

  • Jonathan McConathy1
  • Vadim S. Koshkin2
  • Yusuf Menda3
  • Jordi Ahnert Rodon4
  • Ajit Harishkumar Goenka5
  • Ryan H. Moy6
  • Sophie Morse7
  • Arnaud Demange8
  • Lars Blumenstein9
  • Burcu Babaoğlan10
  • Paola Aimone11
  • Thomas A. Hope12
12 affiliations
  1. 1The University of Alabama at Birmingham 1 Department of Radiology, , Birmingham, Alabama
  2. 2University of California San Francisco 2 Division of Hematology/Oncology, Department of Medicine, , San Francisco, California
  3. 33Department of Radiology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa
  4. 4The University of Texas MD Anderson Cancer Center 4 Department of Investigational Cancer Therapeutics, , Houston, Texas
  5. 5Mayo Clinic in Rochester 5 , Rochester, Minnesota
  6. 6Columbia University Irving Medical Center 6 Division of Hematology/Oncology, Department of Medicine, , New York, New York
  7. 77Novartis Pharmaceuticals Corp., East Hanover, New Jersey
  8. 88Advanced Accelerator Applications, a Novartis Company, Geneva, Switzerland
  9. 99Novartis Biomedical Research, Basel, Switzerland
  10. 1010Novartis Pharmaceuticals UK Ltd, London, United Kingdom
  11. 1111Novartis Pharma AG, Basel, Switzerland
  12. 12University of California San Francisco 12 Department of Radiology and Biomedical Imaging, , San Francisco, California
Open at sourceDOICite

Abstract

PURPOSE: 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). PATIENTS AND METHODS: LuMIERE is a prospective, open-label, nonrandomized, 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 [maximum standardized uptake value (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 (DLT) and treatment-emergent adverse events (TEAE). RESULTS: 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 to be 9.25 GBq. Preliminary Response Evaluation Criteria in Solid Tumors efficacy findings demonstrated a partial response in 1 patient and stable disease in 10 patients (maintained for at least two assessments in 6 patients). CONCLUSIONS: 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.

Related

  1. CAR T cells targeting fibroblast activation protein-α for the treatment of pulmonary fibrosis
    Ying Chen, Qian Zhang, Juanjuan Wu +9
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0Full textGeneral medicineCrossref
  2. Fibroblast Activation Protein Inhibitor Positron Emission Tomography Imaging in Atrial Fibrillation: Current Evidence and Future Perspectives
    Yi Xu, Huiyi Qiu, Chuxian Guo +5
    Reviews in cardiovascular medicinePeer-reviewedCC BYFull textCardiovascular medicineEurope PMC
  3. Targeting fibroblast activation suppresses chemotherapy-induced pro-invasive remodeling of the extracellular matrix
    A. Yui, L. Peng, K. C. Lew +12
    bioRxivPreprintCC BY-NC-NDFull textOncologybioRxiv
  4. Fibroblast Growth Factor 23 and Osteoprotegerin in Vascular Calcification among Patients without Advanced Chronic Kidney Disease
    Keisuke Senda, Nami Teraoka, Kazuma Masuda +6
    Internal MedicinePeer-reviewedCC BY-NC-NDFull textGeneral medicineJ-STAGE
  5. Editorial: The insights of multi-omics into the microenvironment after tumor metastasis: a paradigm shift in molecular targeting modeling and immunotherapy for advanced cancer patients, volume II
    Mengyan Xie, Hong Chang, Xue Zhao +5
    Frontiers in OncologyPeer-reviewedCC BY 4.0Full textOncologyCrossref

Cite

BibTeXRIS
BibTeX
@article{mcconathy2026targeting,
  title = {{Targeting Fibroblast Activation Protein with [177Lu]Lu-FAP-2286 in Patients with Advanced Solid Tumors in the Phase I LuMIERE Trial}},
  author = {Jonathan McConathy and Vadim S. Koshkin and Yusuf Menda and Jordi Ahnert Rodon and Ajit Harishkumar Goenka and Ryan H. Moy and Sophie Morse and Arnaud Demange and Lars Blumenstein and Burcu Babaoğlan and Paola Aimone and Thomas A. Hope},
  journal = {Clinical Cancer Research},
  year = {2026},
  month = jun,
  doi = {10.1158/1078-0432.ccr-25-4356},
  url = {https://doi.org/10.1158/1078-0432.ccr-25-4356},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Targeting Fibroblast Activation Protein with [177Lu]Lu-FAP-2286 in Patients with Advanced Solid Tumors in the Phase I LuMIERE Trial
AU  - Jonathan McConathy
AU  - Vadim S. Koshkin
AU  - Yusuf Menda
AU  - Jordi Ahnert Rodon
AU  - Ajit Harishkumar Goenka
AU  - Ryan H. Moy
AU  - Sophie Morse
AU  - Arnaud Demange
AU  - Lars Blumenstein
AU  - Burcu Babaoğlan
AU  - Paola Aimone
AU  - Thomas A. Hope
PY  - 2026
DA  - 2026/06/01
JO  - Clinical Cancer Research
DO  - 10.1158/1078-0432.ccr-25-4356
UR  - https://doi.org/10.1158/1078-0432.ccr-25-4356
AB  - PURPOSE: 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). PATIENTS AND METHODS: LuMIERE is a prospective, open-label, nonrandomized, 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 [maximum standardized uptake value (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 (DLT) and treatment-emergent adverse events (TEAE). RESULTS: 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 to be 9.25 GBq. Preliminary Response Evaluation Criteria in Solid Tumors efficacy findings demonstrated a partial response in 1 patient and stable disease in 10 patients (maintained for at least two assessments in 6 patients). CONCLUSIONS: 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.
SN  - 1078-0432
SN  - 1557-3265
ER  -