671P - LuMIERE: A phase I/II study evaluating safety, dosimetry, and preliminary activity of [177Lu]Lu-FAP-2286 in patients with advanced solid tumors

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.

Clinical trial identification

NCT04939610.

Editorial acknowledgement

Medical writing support (including development of a draft outline and subsequent drafts in consultation with the authors, collating author comments, copyediting, and fact checking) was provided by Ryan Riley, PhD at Aspire Scientific (Bollington, UK).

Legal entity responsible for the study

Advanced Accelerator Applications, a Novartis company

Funding

Advanced Accelerator Applications, a Novartis company.

Disclosure

J. McConathy: Financial Interests, Research Funding: Cytosite Biopharma, GE Healthcare, Eli Lilly; Financial Interests, Other, Consulting: Blue Earth Diagnostics, GE Healthcare, Eli Lilly, ImaginAb, Novartis, Telix. Y. Menda: Financial Interests, Research Funding, To the institution: Novartis, Perspective Therapeutics, Fusion Pharmaceuticals; Financial Interests, Advisory Board, To the institution: Progenics Pharmaceuticals. J. Rodon: Financial Interests, Personal, Advisory Board: Ellipses Pharma, iOnctura SA, Aadi Bioscience, Envision Pharma, Molecular Partners, Mekanistic, Amgen; Financial Interests, Personal, Other, Consultancy: Clarion Healthcare, Debiopharm, Cullgen, Pfizer, Macrogenics, Oncology One, Columbus Venture Partners, Sardona Therapeutics, Avoro Capital Advisors, Vall d'Hebron Institute of Oncology/Ministero De Empleo Y Seguridad, Chinese University of Hong Kong, Boxer Capital, Llc, Tang Advisors, Llc, Alnylam Pharmaceuticals, Bridgebio Pharma; Financial Interests, Personal, Other, Consultancy/Advisory Board: Monte Rosa Therapeutics, Merus N.V., Incyte; Financial Interests, Institutional, Other, Clinical Research: Novartis, Spectrum Pharmaceuticals, Symphogen, BioAtla, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GSK; Financial Interests, Institutional, Other, Research Funding: Blueprint Medicines, Black Diamond, Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Research Funding/Clinical Research: Hummingbird, Yingli; Financial Interests, Institutional, Research Grant, Research Funding: Vall d'Hebron Institute of Oncology/Cancer Core Europe; Financial Interests, Institutional, Research Grant, Clinical Research: Bicycle Therapeutics, Taiho, Roche Pharmaceuticals, Merus, Curis, AadiBioscience, Nuvation, ForeBio, BioMed Valley Discoveries, Loxo Oncology, Cellestia, Deciphera, Ideaya, Amgen, Tango Therapeutics, Mirati, Linnaeus Therapeutics, Bayer, Hutchinson MediPharma; Other, Other: VHIO/Ministero De Empleo Y Seguridad Social; Other, Travel: European Society for Medical Oncology, Loxo Oncology. A.H. Goenka: Financial Interests, Research Grant, PI on institutional research grant: Sofie Biosciences, Novartis; Financial Interests, Other, Consulting: Bayer Healthcare Llc, Candel Therapeutics, UWorld; Financial Interests, Research Grant, Research grants: NIH; Financial Interests, Research Grant: Mayo Clinic Comprehensive Cancer Center, Champions of Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation, Centene Charitable Foundation, Hoveida Family Foundation. R.H. Moy: Financial Interests, Advisory Board, and consulting: Ideaya Biosciences, Nimbus Therapeutics, PreTech Health ; Financial Interests, Research Funding: Nimbus Therapeutics, Repare Therapeutics. S. Morse: Financial Interests, Other, Employee: Novartis. A. Demange: Financial Interests, Other, Employee: Advanced Accelerator Applications, a Novartis Company; Financial Interests, Stocks/Shares, Stock and stock options: Novartis. P. Aimone: Financial Interests, Other, Employee: Novartis. T.A. Hope: Financial Interests, Research Grant, Grant funding to the institution: Clovis Oncology, GE Healthcare, Janssen, Lantheus, Novartis, Telix Pharmaceuticals, National Cancer Institute, Prostate Cancer Foundation; Financial Interests, Other, Personal fees: Bayer, Blue Earth Diagnostics, Cardinal Health, Lantheus, RayzeBio; Financial Interests, Other, Equity interest in: AdvanCell, Curium.