Interim analysis of TAD: A phase 2 single-arm open-label study of combination therapy of transarterial chemoembolization and ablation with durvalumab in unresectable hepatocellular carcinoma.

e16296 Background: Transarterial chemoembolization (TACE) combined with ablation has been used to treat unresectable hepatocellular carcinoma (HCC) to enhance local tumor control. We initiated the TAD study of TACE in combination with ablation followed by durvalumab to evaluate the safety and efficacy in patients with unresectable HCC. Methods: This phase 2, single-arm study is designed to investigate the safety and efficacy of TACE plus ablation followed by durvalumab in patients with unresectable HCC who are unsuitable for surgical resection. Approximately 30 patients are planned for enrollment. After TACE, patients undergo ablation and then receive durvalumab 1500 mg Q4W until disease progression or death. Patients achieving complete remission (CR) after 1 year of durvalumab discontinue treatment per protocol. Treatment may be extended up to 2 years if imaging shows viable lesions. Tumor assessment is performed according to mRECIST by independent radiologists. The primary endpoint is adverse events of special interest (AESIs). The secondary endpoints are adverse events (AEs), progression-free survival (PFS), Time to progress (TTP) and overall survival (OS). Results: The interim analysis (IA) was conducted. At this IA, 30 patients (SS set) were enrolled, and the cutoff date was 10th Dec 2025. There were 24 patients (FAS and PP set) received TACE plus ablation and at least 1 cycle of durvalumab, with 12 patients receiving durvalumab for ≥1 year. The median follow-up was 27.6 months (range, 11.9-53.0). Among the 30 patients (SS set), 14 (46.7%) reported grade 1–2 AESIs possibly related to durvalumab: 7 (23.3%) elevated liver enzymes, 6 (20.0%) elevated lipase, 4 (13.3%) abnormal thyroid function, 2 (6.7%) elevated amylase, 2 (6.7%) rashes, and 1 (3.3%) interstitial pneumonia. However, only the 1 patient with interstitial pneumonia required oral corticosteroids for management. Additionally, 7 patients (23.3%) reported grade 3 elevated liver enzymes, attributed to TACE or ablation. No grade 4 AEs or AE-related death occurred. Serious AEs were reported in 6 patients (20.0%), none considered treatment related. No patients discontinued durvalumab due to treatment-related AEs (TRAEs). In the PP set, the objective response rate (ORR) was 100% (24/24), including CR in 70.8% (17/24) and PR in 29.2% (7/24). Additionally, the median PFS (events occurred in 15 patients) and TTP were both 12.5 months (95% CI: 9.4–15.6), with a 1-year PFS rate of 58.3%. As of the last follow-up, 2 patients had died of disease progression, and the median OS was not reached. Conclusions: TACE in combination with ablation followed by durvalumab demonstrated an manageable safety profile without unexpected toxicity, and a promising early efficacy in this interim analysis. The trial is ongoing, and OS benefits will be reported with further follow-up. Clinical trial information: NCT04517227 .