Integrin α _v β ₃ -targeted radionuclide therapy with ¹⁷⁷ Lu-AB-3PRGD ₂ in multiple advanced metastatic solid tumors: A prospective, single-arm, single-center, investigator-initiated clinical trial.

Abstract

3009 Background: Tumor angiogenesis drives progression and metastasis in solid malignancies. Integrin α v β 3 is selectively overexpressed on multiple tumor cells and neovasculature with limited normal tissue expression, offering a promising therapeutic target. Our previous dose-escalation study investigated the safety and maximum tolerated dose of the integrin α v β 3 -targeted radiopharmaceutical ¹⁷⁷Lu-AB-3PRGD 2 . Building on this foundation, the current study aims to evaluate its therapeutic efficacy in patients with various advanced metastatic solid tumors. Methods: In this prospective, single-arm, single-center investigator-initiated clinical trial, eligible patients had histologically confirmed advanced metastatic solid tumors with documented progression after exhaustion of standard systemic therapies. Tumor integrin α v β 3 expression was confirmed by 68 Ga-3PRGD 2 PET/CT imaging. Patients received up to four cycles of 177 Lu-AB-3PRGD 2 at 3.7 GBq per cycle. The primary endpoint was ORR by RECIST 1.1. The secondary endpoints included DCR, PFS, OS, and safety. The sample size was calculated based on the primary endpoint of ORR. Assuming a null ORR of 10% and an alternative ORR of 30%, a one-sided binomial test with a significance level (α) of 0.05 and 80% power required approximately 20 evaluable patients. Results: From December 2023 to December 2025, 20 patients were enrolled. Of these, 5 received three treatment cycles and 5 received four cycles. The median age was 62 years (range 38–75) and 30% were female. Tumor types included radioiodine-refractory thyroid cancer (20%), breast cancer (15%), lung cancer (10%), cholangiocarcinoma (10%), renal cancer (10%), and others. At baseline, 65% of patients had ECOG performance status ≥2. Among 13 patients received ≥ 2 cycles of treatment, the ORR was 23% (3/13) and DCR was 92% (12/13), including 3 PR and 9 SD. With a median follow-up of 11.9 months, median PFS was 7.3 months and median OS was 18.5 months. Patients achieving disease control had significantly longer PFS and OS compared to those with progressive disease ( P < 0.001). Dosimetry analysis, available for 18 patients (90%), showed a mean tumor absorbed dose of 6.8 ± 5.4 Gy/GBq. Grade 3/4 treatment-related adverse events occurred in 20% of patients (4/20), primarily hematologic toxicities including thrombocytopenia (n = 4), leukopenia (n = 2), and anemia (n = 2). Conclusions: Integrin α v β 3 -targeted radionuclide therapy with ¹⁷⁷Lu-AB-3PRGD 2 demonstrated promising efficacy in disease control and tumor response, and it was generally well tolerated in patients with advanced metastatic solid tumors. These findings justify further investigation in prospective, multicenter, randomized clinical trials. Clinical trial information: NCT06375564 .