Neoadjuvant systemic chemotherapy combined with camrelizumab (CAM) and apatinib (APA) for BCLC stage A/B hepatocellular carcinoma (HCC) beyond Milan criteria: An interim analysis of a phase 2 trial.

Abstract

e16283 Background: Patients(Pts) in BCLC stage A/B HCC beyond Milan criteria have a high recurrence rate after radical surgery. However, the standardized perioperative treatment strategy has not been established.This study aimed to investigate to efficacy and safety of systemic chemotherapy with mFOLFOX7 regimen combined with camrelizumab (CAM, immune checkpoint inhibitors) plus apatinib (APA, anti-angiogenesis) as conversion therapy for potentially resectable HCC. Methods: In this a prospective, single arm, phase II study, treatment-naive pts with BCLC stage A/B HCC beyond Milan criteria (assessed by MDT as unsuitable for radical resection surgery) were included.The enrolled pts received CAM (200 mg, q3w), APA (250 mg, qd), and mFOLFOX7 (oxaliplatin 85 mg/m 2 , leucovorin 200 mg/m 2 , 5-fluorouracil bolus 400 mg/m 2 on day 1, and 5-fluorouracil infusion 2400 mg/m 2 for 46 hours; q3w; up to 4 cycles). The surgical feasibility of pts was evaluated every 2 cycles . Sequential therapy began 2 weeks after surgery, continuation of CAM and APA was administered for up to 12 months, approximating 17 cycles.The primary endpoint was major pathological reactions (MPR), defined as viable tumor cells in less than 50% of tumor bed. Secondary endpoints were complete pathological reactions (pCR), objective response rate (ORR, by RECIST v1.1 and mRECIST), disease-free survival (DFS), overall survival (OS), and safety. Exploratory endpoint is presence of microvascular invasion (MVI), defined as postoperative histologically confirmed MVI. Results: At the data cut-off (Jan. 20, 2026), a total 21 pts were screened. Among these, 19 pts were enrolled (3 woman and 16 men; median age, 61years; range, 38 - 73 years) and received neoadjuvant therapy. The median tumor size was 71 mm (range, 27 - 147). 17 pts had HBV infection and 9 pts had more than 1 tumors. Out of 19 pts, 13 pts were in follow-up/ finished treatment(4 pts recurrence after surgery), 4 pts withdraw from treatment (inoperability or refusal of surgery), while 2 pts were still receiving CAM plus APA. After a median of 3 (2-4) treatment cycles, 15 pts have undergone hepatic surgery, R0 resection rate was100%, 9 (60.0%) pts achieved MPR. Among pts with MVI, M0 was found in 86.7% (13/15) pts, M1 was found in 13.3% (2/15) pts. 15 pts Hepatic Reserve Function (Indocyanine Green-15min) was normal before hepatic surgery. The most common TEAE included Alanine aminotransferase increased (52.6%), Platelet count decreased (42.1%) and Hypoalbuminemia (42.1%); and Grade 3-4 TRAE occurred in 7 of 19 pts. None of them had Serious Adverse Drug Reactions (SADRs). Conclusions: Neoadjuvant mFOLFOX7 combined with CAM and APA is effective and tolerable in pts with BCLC stage A/B HCC beyond Milan criteria. Preoperative neoadjuvant therapy has reduced the rate of MVI. More data would be further analyzed and reported. Clinical trial information: NCT06607107 .