Phase 1 trial of a new radioligand therapy, [177Lu]Lu-NNS309, in various advanced cancers

Pancreatic cancer (ductal adenocarcinoma of the pancreas, PDAC), non-small cell lung cancer (NSCLC), breast cancer (mammary carcinoma), and colorectal cancer (colorectal carcinoma) are malignant diseases that are often difficult to treat at a locally advanced or metastatic stage. When standard therapies such as chemotherapy, immunotherapy, or targeted therapies are no longer sufficiently effective, new treatment options are needed. This study investigates a novel radioligand therapy using the active agent [177Lu]Lu-NNS309. In this form of treatment, a radioactively labeled molecule is administered as an intravenous infusion; it specifically binds to the fibroblast activation protein (FAP) in tumor tissue and delivers localized radiation there. FAP is produced by cancer-associated connective tissue cells (fibroblasts) and is rarely found in healthy tissue. [177Lu]Lu-NNS309 has not yet been approved for the treatment of cancer.

The objective of this Phase 1 study is to investigate the safety, efficacy, and recommended dose of radioligand therapy with [177Lu]Lu-NNS309. Prior to treatment, a PET/CT or PET/MRI scan using the radiolabeled compound [68Ga]Ga-NNS309 will be performed. This assessment determines whether there is sufficient FAP in the tumor tissue and whether the patients are therefore suitable for treatment with [177Lu]Lu-NNS309. The study is divided into two separate phases. In the first phase (dose escalation), the recommended dose is determined by administering different doses in a stepwise manner. In the second phase (dose expansion), the determined dose is tested in a larger group of patients to gain further insights into safety and initial evidence of efficacy. This is an open-label (unblinded) study with a single treatment arm, meaning that all patients receive the same treatment. The study duration is up to 42 months.

Eligible participants include women and men aged 18 and older with locally advanced or metastatic and inoperable pancreatic cancer, non-small-cell lung cancer, breast cancer, or colorectal cancer, whose disease has progressed following prior treatment, who have been unable to tolerate such prior treatment, or for whom no suitable standard therapy is available. The breast cancer must be either hormone receptor-positive and HER2-negative or triple-negative.