NEO-ERA-01: 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

e16294 Background: High recurrence rate after resection negatively impacts survival outcomes of patients (Pts) with resectable intrahepatic cholangiocarcinoma (ICC). Propensity score-matched analyses suggest neoadjuvant chemotherapy improves overall survival (OS) in patients with resectable ICC exhibiting high-risk factors. This study evaluates the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) combined with Adebrelimab and Lenvatinib in neoadjuvant treatment of resectable ICC with high-risk recurrence factors. Methods: This multi-center, 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 of both neoadjuvant therapy and 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, 2024, 16 Pts (median age 60.5 and 56% male) were enrolled from 3 sites. 11 Pts completed all neoadjuvant therapy (mean 2.3 cycles), followed by surgery. 3 Pts were still undergoing neoadjuvant therapy, and 2 Pts did not undergo surgery: one due to disease progression and the other due to adverse events. According to RECIST 1.1, 14 Pts underwent imaging evaluation. The ORR and DCR were 57.1% and 92.9% respectively (CR:7.1%, PR:50.0%, SD: 35.8%, PD:7.1%). Among 11 Pts, 11(100%) Pts achieved MPR, of which 2(18.2%) Pts achieved pCR. The R0 resection rate was 90.9%. Median size of largest tumor was 7cm and 26% were lymph node positive. 5(31.2%) Pts experienced grade ≥3 treatment-related adverse events, with the most common being hypertension, thrombocytopenia, ALT elevated, GGT elevated and cough. One patient experienced Clavien-Dindo grade 3b complications of wound ulceration. There was zero treatment related mortality. EFS and OS are immature. Conclusions: Neoadjuvant treatment with HAIC (GEMOX), Adebrelimab and Lenvatinib is feasible and safe prior to resection of ICC, without negatively affecting perioperative outcomes. Continued recruitment and follow-up are still ongoing. Clinical trial information: NCT06208462 .