Role of Lu177 FAPI-09 therapy in combination with chemotherapy or immunotherapy for chemo-resistant progressive cancers: Early clinical experience.

Abstract

3094 Background: Chemo resistant progressive tumours represent a major challenge in oncology. These tumours often adapt and develop resistance mechanisms that limit the efficacy of standard treatments. Lu177 FAPI-09 therapy, which targets fibroblast activation protein (FAP) expressed on cancer-associated fibroblasts (CAFs) within the tumor microenvironment, has emerged as a promising treatment option. By binding to FAP, Lu177 FAPI-09 selectively delivers radiation to the tumor stroma, potentially altering the tumor environment and making it more susceptible to subsequent therapies. This study aimed to evaluate the safety, feasibility, and effectiveness of combining Lu177 FAPI-09 therapy with chemotherapy or immunotherapy in patients with advanced chemoresistant cancers. Methods: Eighteen patients with advanced progressive and chemo resistant malignancies were included in this study. All underwent Ga-68 FAPI-09 PET/CT scans prior to treatment to confirm FAP expression in their tumors, ensuring that Lu177 FAPI-09 therapy would be beneficial. The patient group consisted of GI(7), ovarian (11). Prior to Lu177 FAPI-09 therapy, all patients had demonstrated resistance to one or more prior lines of chemotherapy or immunotherapy. Following the administration of Lu177 FAPI-09 therapy, patients received chemotherapy or immunotherapy 5 days later, tailored to their specific tumor type. Disease responses were assessed two months after the combined treatment. Results: After receiving Lu177 FAPI-09 therapy, 80% of patients showed either stable disease or a positive response to the subsequent chemotherapy or immunotherapy. The safety profile of Lu177 FAPI-09 therapy was favourable, with no major grade 3 or 4 adverse events reported. The most common side effects were mild reductions in blood counts, including neutropenia or anaemia. Overall, Lu177 FAPI-09 therapy in combination with chemotherapy or immunotherapy was well-tolerated by the majority of patients. Conclusions: Lu177 FAPI-09 therapy, when used in combination with chemotherapy or immunotherapy, shows promise in enhancing treatment responses in patients with chemo resistant progressive cancers with minimal side effects and no major toxicities. The use of Ga-68 FAPI-09 PET/CT scans to identify patients with tumors expressing FAP ensures appropriate patient selection, optimizing the likelihood of a positive outcome. These findings suggest that Lu177 FAPI-09 therapy could be an effective approach to overcome resistance and improve treatment outcomes in patients with advanced malignancies.