An exploratory study:Cadonilimab(AK104) and Lenvatinib combined with stereotactic body radiotherapy in the conversion therapy of potentially resectable hepatocellular carcinoma

Abstract

Background Surgery is one of the standard treatments for long-term survival in patients with hepatocellular carcinoma(HCC). However, the majority of HCC patients are initially diagnosed at an advanced stage, less than 30% of patients can undergo curative resection, and the risk of postoperative recurrence is usually more than 50%. Conversion therapy creates the opportunity for radical resection of potentially resectable HCC, but its exact protocol and effectiveness remain controversial. As a first-line systematic treatment for advanced HCC, immunocombined targeted therapy has shown good efficacy. Studies have shown that some patients can obtain surgical resection opportunities through radiotherapy, and radiotherapy combined with immunotherapy has also shown good clinical benefits in conversion therapy trials. Therefore, this study aims to explore the efficacy and safety of Cadonilimab(AK104) and Lenvatinib combined with Stereotactic body radiotherapy(SBRT) in HCC conversion therapy, which may provide a new therapeutic strategy for HCC patients in the future. Methods/design: An exploratory clinical study is planned to enroll 27 patients with potentially resectable HCC. Eligible patients underwent tumor evaluation before receiving Cadonilimab(AK104) and Lenvatinib combined with SBRT conversion therapy, after the second cycle of treatment, and before surgery, and were followed up every 6 weeks after surgery. The primary endpoint was objective response rate(ORR), and secondary endpoints were surgical resection rate, major pathological response(MPR), duration of response(DOR), disease control rate(DCR), progression-free survival(PFS), time to disease progression(TTP), and overall survival(OS), and adverse events(AEs). Discussion This trial will evaluate the efficacy and safety of Cadonilimab(AK104) and Lenvatinib combined with SBRT in the conversion therapy of potentially resectable HCC patients, providing clinical data for a new mode of conversion therapy for HCC, combining immune and targeted therapy with radiotherapy. At present, there is no consensus standard protocol for HCC conversion therapy, and more prospective studies are needed to further explore the treatment modalities and their effects. Trial registration: Chinese Clinical Trial Registry: ChiCTR2300068781, Registered on February 28, 2023.