Evaluation of the radioactively labeled investigational drug 177Lu-DFC413 in patients with advanced solid tumors

Solid tumors are cancers that form a firm mass of tissue, as opposed to cancers of the blood and bone marrow. If metastases have already formed in other parts of the body, the standard treatment options—depending on the disease—include chemotherapy, immunotherapy, or targeted therapies. For hormone receptor-positive, HER2-negative breast cancer. After several prior treatment regimens, it may happen that no suitable standard therapy is available anymore. In such situations, new treatment approaches are being investigated. The investigational drugs in this study are based on the principle of radioligand therapy. A carrier molecule is coupled with a radioactive atom and is designed to specifically bind to certain structures in the tumor tissue, thereby delivering the radioactive atom directly to the tumor. Lutetium-177 in the therapeutic investigational drug 177Lu-DFC413 emits primarily short-range beta radiation as it decays, which is intended to damage the genetic material (DNA) of cells in the immediate vicinity. Gallium-68 in the diagnostic investigational drug 68Ga-NNS309, on the other hand, is only weakly and briefly radioactive and can be visualized using positron emission tomography (PET). Such radioactively labeled agents are typically administered through a vein (intravenously).

This Phase 1 study is the first to investigate 177Lu-DFC413 in humans. The study consists of two phases. First, all patients undergo imaging with 68Ga-NNS309 and are examined using PET in combination with computed tomography (CT) or magnetic resonance imaging (MRI). Only patients whose tumor lesions take up 68Ga-NNS309 are subsequently eligible for treatment with 177Lu-DFC413. A dose-finding phase with various dose levels is followed by an expansion phase with study groups organized by tumor type; the study will evaluate safety and tolerability, the distribution of the radiation dose in the body (dosimetry), the imaging properties of 68Ga-NNS309, and initial indications of whether 177Lu-DFC413 can affect the tumors. There is only one study group with no comparison group (uncontrolled) and, therefore, no random assignment (non-randomized). The study is open-label (unblinded). This means that both the patients and the study physicians are aware of the treatment.

Eligible participants include women and men aged 18 and older with a locally advanced, inoperable, or metastatic tumor whose disease has progressed following prior treatment or who have been unable to tolerate such treatment, and whose tumor lesions take up 68Ga-NNS309. These include pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), hormone receptor-positive, HER2-negative ductal and lobular breast cancer (HR+/HER2-, with binding sites for female sex hormones but without elevated HER2 expression), triple-negative breast cancer (TNBC, lacking both characteristics), colorectal cancer, and soft tissue sarcomas. Patients with soft tissue sarcoma can only be enrolled in the extension phase. Gastrointestinal stromal tumors (GIST) and Kaposi’s sarcoma are excluded. Patients who have already received radioligand therapy are ineligible to participate.