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.

e16297 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, anti-PD-1 antibody) plus apatinib (APA, anti-angiogenesis) as conversion therapy for potentially resectable HCC. Methods: In this prospective, single arm, phase II study, treatment-naive adult 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 6 cycles). The surgical feasibility of pts was evaluated every 2 cycles. Sequential therapy began 2 weeks after surgery. CAM and APA were given for up to 12 months or approximately 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. 25, 2025), a total 14 patients were screened. Among these, 12 pts were enrolled (3 woman and 9 men; median age, 61.5 years; range, 38 - 73 years) and received neoadjuvant therapy. The median tumor size was 82.5 mm (range, 44 - 147). 12 pts had HBV infection and 3 (25%) pts had more than 1 tumors. With a median follow-up of 7.2 months (95% CI: 0.6 - 13.7), no progression or death event occurred. Out of 12 patients, 7(58.3%) were in follow-up/ finished treatment, while 5 (41.7%) patients were still receiving CAM plus APA. After a median of 3 (2-4) treatment cycles, 1 pts achieved PR but refused surgery, 11 pts underwent hepatic resection. R0 resection rate was 100%, 7 (63.6%) pts achieved MPR. Among pts with MVI, M0 was found in 81.8% (9/11) pts, M1 was found in 18.2% (2/11) pts. The most common AEs included increased alanine aminotransferase (58.3%), decreased neutrophil count (41.6%) and diarrhea (41.6%); and Grade 3-4 AEs occurred in 1 of 12 patients. None of them had Serious Adverse Drug Reactions (SADRs). Conclusions: Neoadjuvant mFOLFOX7 combined with Camrelizumab and Apatinib 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: NCT06670107 .