177Lu-LNC1004 Radioligand Therapy in Patients with End-stage Metastatic Cancers: A Single-Center, Single-Arm, Phase II Study
Mené sur 28 patients atteints de tumeurs métastatiques progressives et présentant une expression élevée de la protéine d'activation des fibroblastes (FAP), cet essai de phase II évalue l'efficacité, du point de vue de la réponse radiologique post-traitement, et la sécurité d'une thérapie par radioligand à base de 177Lu-LNC1004
Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and certain tumor cells, making it a promising therapeutic target for various malignancies. This study evaluated the efficacy and safety of 177Lu-Evans blue–FAP inhibitor (177Lu-LNC1004) radioligand therapy (RLT) for treating end-stage metastatic tumors.This single-arm, single-center, phase II trial included 28 patients with progressive metastatic malignancies (11 types) and high FAP expression (defined as a maximum standardized uptake value ≥10 in >50% of tumors) who had exhausted all approved therapies, screened between June 2022 and April 2024. Patients were scheduled to receive four 177Lu-LNC1004 RLT cycles at 3.33 GBq/cycle every 6 weeks. The primary endpoint was post-RLT radiologic response. The secondary endpoints were progression-free survival (PFS), overall survival (OS), dosimetry, and safety.Eastern Cooperative Oncology Group scores >2 were observed in 68% of patients. Overall, 63 177Lu-LNC1004 RLT cycles were performed, with 19 (68%) patients undergoing ≥2 cycles. Disease control was achieved in 13 (13/28, 46%) patients, with 4 and 9 patients demonstrating partial response and stable disease, respectively, and associated with improved PFS and OS (P < 0.001). The mean absorbed dose in tumors was 4.69 ± 3.83 Gy/GBq (1.18–25.03 Gy/GBq). Treatment-related grade 3/4 hematotoxicity was observed in six (21%) patients, with thrombocytopenia, leukopenia, and neutropenia most prevalent. No grade 3/4 hepatotoxicity or nephrotoxicity was observed.FAP-directed RLT using 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated with an acceptable toxicity profile. Nearly half of patients achieved disease control, which was associated with prolonged PFS and OS.