Neo-adjuvant tislelizumab combined with lenvatinib treatment for resectable, recurrent hepatocellular carcinoma.

517 Background: The persistent challenge of elevated re-recurrence rates following secondary hepatectomy complicates the prospects for improving survival in recurrent hepatocellular carcinoma (rHCC) patients. Immunotherapy combined with targeted drugs have been the first-line therapy for advanced HCC and shown good response rate in neoadjuvant situation. However, the effectiveness and safety of the combination treatment has not been reported in rHCC patients. To address this, we conducted the present phase 2 clinical trial of neoadjuvant treatments using tislelizumab in combination with lenvatinib for rHCC patients. Methods: Patients with resectable rHCC patients who had previously undergone curative treatment were enrolled. Enrolled patients were treated with 2 neoadjuvant cycles of a combination of tislelizumab 200mg intravenously every 3 weeks and lenvatinib 8mg every day (12mg for patients over 60kg) for 4 weeks. Hepatectomy was conducted in six weeks after enrollment. One month after surgery, adjuvant combination of tislelizumab and lenvatinib was started for at least one year or until disease progression or intolerance of adverse reactions. The primary objective of the trial is to evaluate one-year disease-free survival (DFS) rate, and secondary endpoints include objective response rate (ORR) as assessed by RECIST 1.1, major pathologic response (defined as over 90% tumor necrosis), and safety considerations. Results: Until Sep 30 th , 2023, a total of 14 patients have been enrolled. All participants underwent the complete neoadjuvant therapy with a combination of tislelizumab and lenvatinib before proceeding to hepatectomy. Throughout the neoadjuvant phase, 14.3% (2/14) of patients occurred adverse events below grade 3, with no severe adverse events occurring. The most common adverse events were fatigue (in 2 patients), hypertension (in 1 patient) and reduced appetite (in 1 patient). In 14 patients, 12 patients underwent R0 resection and 2 were waiting for hepatectomy. The average time from the initiation of the neoadjuvant therapy to hepatectomy was approximately 40.42 days. On the radiological front, one patient (8.3%) exhibited a partial response, while 11/12 (91.7%) displayed stable disease with 8 patients had tumor shrinkage. In terms of pathological outcomes, 25% of patients (3/12) achieved a complete response, whereas the remaining patients showed varying degrees of pathologic response, ranging from 5% to 85%. Conclusions: In summary, the dual therapy of tislelizumab and lenvatinib demonstrates encouraging safety and effectiveness as a neoadjuvant intervention for patients with rHCC. The long-term results of this combined treatment approach are eagerly anticipated. Clinical trial information: NCT04615143 .