Abstract
671P LuMIERE: A phase I/II study evaluating safety, dosimetry, and preliminary activity of [177Lu]Lu-FAP-2286 in patients with advanced solid tumors
Annals of oncology, Vol.35(Supplement 2), pp.S526-S526
09/2024
DOI: 10.1016/j.annonc.2024.08.737
Abstract
Background
Fibroblast activation protein (FAP) is highly expressed on the surface of cancer-associated fibroblasts and has limited expression in normal tissues. [177Lu]Lu-FAP-2286, an investigational radioligand therapy, has shown antitumor activity in preclinical models. LuMIERE is a phase 1/2 open-label study of [177Lu]Lu-FAP-2286 in patients (pts) with advanced FAP-expressing solid tumors.
Methods
Eligible pts for phase 1 had advanced/metastatic solid tumors, were refractory to or had progressed following prior therapy, and had [68Ga]Ga-FAP-2286 uptake in tumoral lesions (PET imaging). A Bayesian optimal interval design included 4 dose escalation levels (starting dose 3.7 GBq; maximum dose 9.25 GBq). Pts received ≤6 cycles every 6 weeks. Dosimetry and safety were assessed after each dose. Primary endpoints were dose-limiting toxicities (DLTs), adverse events (AEs), and clinical laboratory abnormalities. Efficacy was investigator-assessed objective response by RECIST v 1.1.
Results
Of 35 pts enrolled and imaged, 27 were treated (median age 60 years; 52% male). The most common tumors were pancreatic (n=9), colorectal (n=4), and head and neck (n=3). Overall, 14 pts experienced treatment-related AEs, with Grade ≥3 events observed in 2 pts (one event each). Two DLTs were observed: Grade 4 lymphopenia (dose 5.55 GBq; Grade 2 at screening) and Grade 3 hemoptysis (dose 9.25 GBq; lung metastases containing pseudoaneurysms at screening). There were no Grade ≥3 decreases in neutrophil, hemoglobin, or platelet levels over time. Overall, 1 Grade ≥3 AE was reported following imaging with [68Ga]Ga-FAP-2286 (small intestine obstruction), which was not considered treatment related. Best response included partial response in 1 pt and stable disease in 9 pts. The recommended phase 2 dose of [177Lu]Lu-FAP-2286 was declared as 9.25 GBq. Dosimetry data will be presented at ESMO.
Conclusions
[177Lu]Lu-FAP-2286 was well tolerated in heavily pretreated pts with a low incidence of DLTs and Grade ≥3 AEs observed, supporting the commencement of phase 2 and planned combination therapies.
Details
- Title: Subtitle
- 671P LuMIERE: A phase I/II study evaluating safety, dosimetry, and preliminary activity of [177Lu]Lu-FAP-2286 in patients with advanced solid tumors
- Creators
- J. McConathy - University of Alabama at BirminghamY. Menda - University of IowaJ. Rodon - The University of Texas MD Anderson Cancer CenterA.H. Goenka - Mayo ClinicR.H. Moy - Columbia University Irving Medical CenterS. Morse - Global Drug Development, Novartis Pharmaceuticals Corp, East Hanover, NJ, USAA. Demange - Advanced Accelerator Applications (Italy)P. Aimone - Novartis (Netherlands)T.A. Hope - University of California, San Francisco
- Resource Type
- Abstract
- Publication Details
- Annals of oncology, Vol.35(Supplement 2), pp.S526-S526
- DOI
- 10.1016/j.annonc.2024.08.737
- ISSN
- 0923-7534
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 09/2024
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984708761602771
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