Phase I/II, first-in-human study of yttrium-90 carbon microspheres in patients with unresectable hepatocellular carcinoma: Safety and early efficacy profiles.

4169 Background: Yttrium-90 microsphere selective internal radiation therapy (Y-90 SIRT) plays a significant role in the treatment of unresectable hepatocellular carcinoma. The phase I clinical study evaluated the safety and efficacy of Y-90 Carbon Microspheres Injection in patients with unresectable hepatocellular carcinoma. Methods: This multicenter, single-arm, prospective study was conducted across eight centers in China. It enrolled all eligible patients with uHCC who underwent radioembolization between 2023 and 2024. Eligibility criteria included unresectable hepatocellular carcinoma, Child-Pugh A cirrhosis, and an Eastern Cooperative Oncology Group performance status of 0-1. The primary endpoints included the incidence of adverse events and serious adverse events post-infusion, and the objective response rate in the treated area at first assessment according to mRECIST criteria. Among the 40 enrolled patients, 40.0% had an ECOG status of 0. According to China Liver Cancer Staging (CNLC), there were 12 cases (30.0%) in stage Ia, 9 cases (22.5%) in stage Ib, 6 cases (15.0%) in stage IIa, 4 cases (10.0%) in stage IIb, and 9 cases (22.5%) in stage IIIa of liver cancer. The median tumor size was 55.36 mm (range: 11.2–141.2). Results: All subjects received radioembolization as primary treatment, with a median tumor target absorbed dose of 450 Gy (range: 196.5 Gy-2000 Gy). According to the SPECT/CT results after treatment with NRT6003 injection, the median tumor absorbed dose was 429.93 Gy (range: 197.1 Gy-2827.7 Gy). As of February 21, 2025, the median follow-up of 9.5 months, a total of 221 treatment-related adverse events were reported, including 16 events of grade ≥3 and 2 serious adverse events (Upper abdominal pain, gastrointestinal bleeding). The best overall objective response rates were 92.5% (37/40) for whole-body and 97.5% (39/40) for local responses. The confirmed objective response rates were 82.5% (33/40) for whole-body and 85% (34/40) for local assessments. Six patients were re evaluated for surgical treatment due to tumor shrinkage. Conclusions: In this multicenter Y-90 SIRT study, treatment with Y-90 Carbon Microspheres demonstrated a favorable safety and efficacy were observed in the treatment of unresectable HCC, providing a highly promising treatment option. Clinical trial information: NCT06310590 .