Investigation of the targeted radioactive agent LY4337713 in patients with advanced solid tumors with confirmed FAP (FiREBOLT study)

Advanced-stage cancers can spread to other organs (metastasize) and are often difficult to treat. Many tumors are surrounded by so-called cancer-associated connective tissue cells (fibroblasts) that promote tumor growth. These cells carry a specific protein on their surface, the fibroblast activation protein (FAP), which is rarely found in healthy tissue but is detectable in elevated amounts in many solid tumors. LY4337713 is a novel targeted radioligand therapy that specifically binds to FAP in tumor tissue and releases radioactive radiation there, thereby specifically damaging the tumor cells. The drug is administered as an intravenous infusion and has not yet been approved for the treatment of cancer. Before starting therapy, clinical findings or imaging tests are used to verify whether the tumor tissue actually contains FAP, since the treatment is specifically targeted against this protein.

The goal of the Phase 1 study is to investigate the safety and tolerability, as well as initial evidence of efficacy, of the new radioligand therapy LY4337713 in patients with advanced solid FAP-positive tumors. The study is divided into two parts. In the first part (Phase 1a), increasing doses of the drug will be tested to determine the maximum safe dose. To this end, the occurrence of so-called dose-limiting toxicities (DLTs) will be monitored within the first 28 days of treatment. In addition, the study will examine how the active ingredient and the delivered radiation dose are distributed throughout the body. To this end, blood samples are taken regularly during the study, and the concentration of the active ingredient in the blood is measured. In the second part (Phase 1b), LY4337713 is further investigated in tumor-specific cohorts to assess its efficacy against various types of cancer. To this end, the so-called objective response rate (ORR) will be determined. The study will measure whether the tumors completely regress or shrink significantly under the therapy. The assessment will be based on standardized imaging examinations. The study is open-label, meaning that both the patients and the study physicians know which group assignment applies and what is being administered. In this study, assignment to the cohorts is not random (non-randomized); all patients receive the study medication. Participation in the study is expected to last about 5 years.

Patients aged 18 years or older with advanced or metastatic breast cancer, ovarian cancer, pancreatic cancer, colorectal cancer, esophageal cancer, stomach cancer, bile duct cancer, or other FAP-positive solid tumors are eligible to participate. A prerequisite is that patients have already received prior treatment for their advanced or metastatic disease; the type and number of prior treatments depend on the tumor type and the study arm.