[225Ac]Ac‑LNC1011 / Dongcheng Pharma, National University of Singapore - LARVOL DELTA

Synthesis and preliminary evaluation of [225Ac]Ac‑LNC1011 for targeted α-radionuclide therapy of prostate cancer (SNMMI 2025) - "[225Ac]Ac-LNC1011 was successfully radiolabeled with high radiochemical purity and high stability within 96 h (radiochemical purity >96%). The high binding affinity of LNC1011 (IC50 = 16.28 nM) to PSMA is slightly higher than that of PSMA-617 (IC50 = 27.93 nM). Biodistribution studies confirmed that [225Ac]Ac-LNC1011 had moderate blood elimination half-life (T1/2z = 13.4 ± 0.57 h), which was at an optimized level between [225Ac]Ac-PSMA-617 (T1/2z = 5.19 ± 0.12 h) and [225Ac]Ac-PSMA-EB-01 (T1/2z = 25.18 ± 2.78 h)."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Synthesis and preliminary evaluation of [225Ac]Ac‑LNC1011 for targeted α-radionuclide therapy of prostate cancer (SNMMI 2025) - "[225Ac]Ac-LNC1011 was successfully radiolabeled with high radiochemical purity and high stability within 96 h (radiochemical purity >96%). The high binding affinity of LNC1011 (IC50 = 16.28 nM) to PSMA is slightly higher than that of PSMA-617 (IC50 = 27.93 nM). Biodistribution studies confirmed that [225Ac]Ac-LNC1011 had moderate blood elimination half-life (T1/2z = 13.4 ± 0.57 h), which was at an optimized level between [225Ac]Ac-PSMA-617 (T1/2z = 5.19 ± 0.12 h) and [225Ac]Ac-PSMA-EB-01 (T1/2z = 25.18 ± 2.78 h)."

Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

First-in-human study of 225Ac-LNC1011 in patients with prostate-specific membrane antigen (PSMA) positive prostate cancer (SNMMI 2025) - "The details were 3.7 MBq /cycle (×2 cycles) in 3 patients and 5.5 MBq /cycle (×1 cycle) in 1 patient, and the patients had previously received 177Lu-PSMA-617 therapy, with a median age of 71.5 years (range: 66–82 years). Administration of 225Ac-LNC1011 was well tolerated, with no grade II/III/IV renal, hematologic, or salivary gland toxicity observed in any of the patients. All patients were alive at the last follow-up. PSA levels decreased in 3 patients after treatment (from 7.885 ng/mL to 0.185 ng/mL; from 6.034 ng/mL to 1.016 ng/mL; and from 353.395 ng/mL to 310.238 ng/mL) (1 patient was scheduled for a PSA testing in the near future)."

Clinical • P1 data • Genito-urinary Cancer • Musculoskeletal Pain • Oncology • Pain • Prostate Cancer • Solid Tumor

Novel Targeted Therapy Shows Promise in PSMA-Positive Prostate Cancer (Cancer Network) - P1 | N=20 | ChiCTR2500095162 | "According to RECIST v1.1 criteria, the objective response rate (ORR) was 50%, with 2 patients achieving partial responses (PRs) and 2 patients having stable disease. According to PERCIST v1.0 guidelines, the ORR was 75%, with 3 patients achieving PRs and 1 having stable disease. The imaging from baseline and the last follow-up were used for the efficacy evaluation....The median progression-free survival (PFS), with follow-up times of 12 months, 12 months, 6 months, and 6 months, were all yet to be reached. Of the four patients, their respective ECOG performance statuses at baseline were 1, 2, 2, and 2; after treatment, they were 0, 1, 3, and 1. It was noted that the third patient developed a respiratory infection and experienced a progressive decline in their general condition. In March 2025, the patient died, and the death was not considered to be related to 225Ac-LNC1011."

P1 data • Prostate Cancer