NEO-ERA-01(CLEAP2507): A multi-center, single-arm, phase II study with neoadjuvant therapy of HAIC (GEMOX) combined with adebrelimab and lenvatinib for resectable intrahepatic cholangiocarcinoma with high-risk recurrence factors.

Abstract

e16295 Background: The high recurrence rate after resection compromises survival in patients with resectable intrahepatic cholangiocarcinoma (ICC). Propensity score–matched studies indicate that neoadjuvant chemotherapy improves overall survival (OS) in high-risk resectable ICC. This study evaluates the efficacy and safety of neoadjuvant hepatic artery infusion chemotherapy (HAIC) combined with adebrelimab and lenvatinib in this population. Methods: This multicenter, single-arm, phase II trial was conducted for Pts with resectable, high-risk ICC, defined as tumor size > 5 cm, multiple tumors, presence of radiographic major vascular invasion, or lymph node involvement. Pts received 2-4 cycles of neoadjuvant therapy, consisting of HAIC-GEMOX (Oxaliplatin 85mg/m 2 and Gemcitabine 800mg/m 2 on Days 1 Q3W), Adebrelimab (1200mg on Days 3 Q3W) and Lenvatinib (8mg on Days 5-21 Q3W), followed by curative-intent surgical resection. The primary endpoint was completion rate of study treatment，defined as proportion of patients receive both neoadjuvant therapy and subsequently curative-intent surgical resection. Secondary endpoints included safety, R0 resection, OS, objective response rate (ORR), event-free survival (EFS), complete pathological response (pCR) and major pathological response (MPR) defined as ≤50% residual viable tumor cells in resection bed. Results: As of January 15, 2026, 31 Pts (median age 58 and 58% male) were enrolled from 4 sites in China. 27 Pts completed all neoadjuvant therapy (mean 2.5 cycles), followed by surgery. 1 Pts were still undergoing neoadjuvant therapy, and 3 Pts did not undergo surgery: one due to disease progression, one due to adverse events and another chronic heart failure. According to RECIST 1.1, 30 Pts underwent imaging evaluation. The ORR and DCR were 43.3% and 93.3% respectively (CR:3.3%, PR:40.0%, SD: 50%, PD:6.7%). Among 27 Pts, 25 (92.6%) Pts achieved MPR (2 Pts achieved pCR). The R0 resection rate was 96.3%. Median size of largest tumor was 5.9 cm and 44.4% were lymph node positive. 11 (35.5%) Pts experienced grade 3 treatment-related adverse events, with the most common being hypertension, thrombocytopenia, ALT elevated, GGT elevated and cough, with no grade 4/5 adverse events. One patient experienced Clavien-Dindo grade 3b complications of wound ulceration. No treatment-related mortality occurred. EFS and OS are immature. Conclusions: Neoadjuvant HAIC (GEMOX) combined with adebrelimab and lenvatinib showed good feasibility, acceptable safety, and promising pathological responses in high-risk resectable ICC. Perioperative safety was not compromised. Long-term survival outcomes require ongoing follow-up. Clinical trial information: NCT06208462 .