In this study, researchers present data on the efficacy and safety of 90Y-labeled FAPI-46 (90Y-FAPI-46-RLT) in patients with advanced sarcoma, pancreatic cancer, and other cancer entities. Patients with advanced metastatic cancer, no more effective treatment options, and high fibroblast activation protein (FAP) expression were administered up to 4 cycles of radioligand therapy (RLT) SUVmax more than or equal to 10 in more than 50% of the tumor. The primary endpoint was the RECIST response after RLT. Secondary endpoints included PET response (PERCIST), overall survival (OS), dosimetry, and safety of FAP-RLT. Among 119 screened patients, 21 (18%) were found eligible [n=16/3/1/1 sarcoma/pancreatic cancer/prostate/gastric cancer; 38% Eastern Cooperative Oncology Group (ECOG) ≥ 2] and received 47 90Y-FAPI-46-RLT cycles; 16 of 21 (76%) patients underwent repeat RLT. By RECIST, disease control was confirmed in 8 of 21 patients [38%; 8/16 (50%) of evaluable patients). There was one partial response (PR) and 7 stable diseases after RLT. Disease control was associated with prolonged OS (P=0.013). PERCIST response was noted in 8 of 21 patients [38%; 8/15 (53%) of evaluable patients]. The dosimetry was acquired in 19 (90%) patients. The mean absorbed dose was 0.53 Gy/GBq in the kidney, 0.04 Gy/GBq in bone marrow, and less than 0.14 Gy/GBq in liver and lung. Treatment-related grade 3 or 4 adverse events were observed in 8 (38%) patients with thrombocytopenia (n = 6) and anemia (n = 6) the being most prevalent. 90Y-FAPI-46-RLT was safe and led to RECIST PR in 1 case as well as stable disease in about 1/3 of patients with initially progressive sarcomas, pancreatic cancer, and other cancers.