LUMIERE (Phase I/II)

Investigator physician: Dr Boursier Caroline

A Phase 1/2, Multicenter, Open-label, Non-randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry,and Preliminary Activity of [¹⁷⁷Lu]Lu-FAP-2286 in Participants with an Advanced Solid Tumor

Solid tumors

Fibroblast activation protein (FAP) is a cell surface protein that is highly expressed on the surface of cancerassociated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers, whereas limited expression of FAP is observed in normal tissues. In some cancers of mesenchymal origin, notably sarcoma and mesothelioma, FAP expression has also been observed on the tumor cells themselves. Given the restricted expression profile, FAP is a promising target for peptide-targeted radionuclide imaging and therapeutic agents.

FAP-2286 is a peptide (that potently and selectively binds to FAP) attached to a linker and 1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) cage available for carrying a radionuclide for imaging or therapeutic applications.

The investigational imaging agent, [⁶⁸Ga]Ga-FAP-2286, contains the positron emitter gallium-68 that allows FAP-expressing solid tumors to be imaged by positron emission tomography (PET) scanning.

The investigational therapeutic agent, [¹⁷⁷Lu]Lu-FAP-2286, contains the beta minus emitter lutetium 177 High-affinity binding of FAP-2286 to FAP-expressing cells in solid tumors allows targeted delivery of the Lu- 177 radionuclide. Lu-177 undergoes radioactive decay to emit beta minus radiation, which causes DNAdamage and consequently death to CAFs and cancer cells.

Phase 1 of this study is designed to evaluate the safety and establish the recommended intravenous (IV) Phase 2 dose (RP2D) for [¹⁷⁷Lu]Lu-FAP-2286 monotherapy in participants with FAP-expressing solid tumors. Phase 2 is designed to evaluate the safety and efficacy of [¹⁷⁷Lu]Lu-FAP-2286 as monotherapy in participants with pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and breast cancer (BC) and in combination with chemotherapy in participants with untreated PDAC or relapsed NSCLC. Participants in both Phase 1 and 2 will be selected for treatment with [¹⁷⁷Lu]Lu-FAP-2286 based on [⁶⁸Ga]Ga-FAP-2286 imaging for determining tumor FAP expression.

Imaging: [⁶⁸Ga]Ga-FAP-2286
Therapeutic agent: [¹⁷⁷Lu]Lu-FAP-2286
Study status: Recruiting
Clinical Trial number: NCT04939610
Funding: