Fibroblast Activating Protein (FAP)-Targeted Radiopeptide Therapy using ¹⁷⁷Lu-, ²²⁵Ac- and ⁹⁰Y-labeled 3BP-3940 in Diverse Advanced Solid Tumors: First-in-Humans Results

Ziel/Aim The purpose of this study was to determine the feasibility of using a novel FAP-targeted cyclic peptide 3BP-3940 for peptide targeted radionuclide therapy (PTRT) and present first-in-humans results using ¹⁷⁷Lu, ⁹⁰Y and ²²⁵Ac labeled 3BP-3940 in end-stage cancer patients.

Methodik/Methods 24 patients (14 men; mean age 59.3±9.5 years) with advanced metastatic cancers of the pancreas (PDAC), breast, lung, esophagus, hepatocellular, appendix, ovary, and bowel sarcoma presented with disease progression after previous treatments and were treated with PTRT between March 2021 and October 2022. Pre-treatment PET/CT imaging was done with Ga-68 3BP-3940 to determine tumor uptake. CTCAEv.5.0. was used to grade toxicity. Kaplan–Meier survival analysis was performed to calculate overall survival (OS), defined from the start of PTRT.

Ergebnisse/Results Cumulative activity was for ¹⁷⁷Lu 13.5±11.6 GBq (n=16; up to 37.1 GBq), ⁹⁰Y 11.2±8 GBq (n=7; up to 25.7 GBq), and ²²⁵Ac 15.2±8.5 MBq (n=21; up to 33 MBq). Visual analysis of posttherapy whole-body scans and SPET/CT scans demonstrated significant uptake and retention of 3BP-3940 in tumor lesions in all patients. After the first cycle, responses were progressive disease (n=10, 42%), partial remission (n=7, 29%), mixed pattern (n=2, 8%), stable disease (n=2, 8%) and to-be evaluated (n=2, 8%). For the entire cohort from the start of PTRT (n=24), the median OS was 12.0 months. In the subgroup of patients with advanced PDAC (n=7), the median OS was 9.5 months.

Schlussfolgerungen/Conclusions 3BP-3940 PTRT is feasible with ¹⁷⁷Lu/⁹⁰Y/²²⁵Ac either alone or as TANDEM treatment of end-stage cancer patients. Treatments were well-tolerated without significant adverse effects. 3BP-3940 PTRT demonstrated a favorable biodistribution, significant uptake and retention in tumor lesions with very high tumor-to-background ratio, and should objective responses in advanced metastatic adenocarcinomas and sarcomas. The survival benefit for PDAC patients seems to be very promising.

Publication History

Article published online:
30 March 2023