Cadonilimab Plus Lenvatinib Combined with Stereotactic Body Radiotherapy for Conversion Therapy in Unresectable or Potentially Resectable Hepatocellular Carcinoma: A Study Protocol.

backgroundConversion therapy offers a critical opportunity to convert potentially resectable hepatocellular carcinoma (HCC) to surgically resectable status; yet, its optimal protocol and efficacy remain unstandardized and controversial. As a first-line systemic treatment for advanced HCC, immunotherapy combined with targeted therapy has demonstrated robust antitumor activity. Accumulating evidence suggests that radiotherapy can render some unresectable HCC patients amenable to surgical resections. Given these advancements, this study aims to investigate the efficacy and safety of cadonilimab (a dual immune checkpoint inhibitor targeting PD-1 and CTLA-4) plus lenvatinib (a multi-targeted tyrosine kinase inhibitor) combined with stereotactic body radiotherapy (SBRT), with the goal of achieving conversion therapy for potentially resectable HCC and prolonging survival for unresectable HCC.

methodsThis is a single-arm, single-center exploratory cohort study designed to enroll 27 HCC patients who meet the following eligibility criteria: surgically unresectable China Liver Cancer Staging (CNLC) stage Ia, Ib, or IIa, or surgically resectable CNLC stage IIb or IIIa. Eligible patients will undergo comprehensive tumor evaluation at three key time points: pre-conversion therapy (cadonilimab + lenvatinib + SBRT), after the second treatment cycle, and preoperatively. Postoperatively, patients will be followed up every six weeks for long-term efficacy and safety monitoring. The primary endpoint is the objective response rate (ORR), assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST) criteria; in case of inconsistent results between the two criteria, mRECIST will serve as the primary reference. Secondary endpoints include surgical resection rate, major pathological response (MPR) rate, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), time to disease progression (TTP), overall survival (OS), and the incidence and severity of treatment-related adverse events (AEs). AEs will be graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 and coded using the Medical Dictionary for Regulatory Activities (MedDRA), respectively. DISCUSSION: This study is designed to evaluate the efficacy and safety of cadonilimab combined with lenvatinib and SBRT for conversion therapy in patients with potentially resectable HCC. By integrating dual immune checkpoint inhibition, anti-angiogenic targeted therapy, and high-precision local radiotherapy, this regimen leverages synergistic antitumor effects to address the unmet clinical need for optimized conversion strategies in HCC. This exploratory trial will provide critical clinical evidence for this novel triple-combination conversion therapy, enriching treatment options for patients with potentially resectable or technically unresectable HCC. The findings are expected to lay a solid foundation for future large-scale, multi-center randomized controlled trials to further validate the clinical value of this regimen.

trial registrationChinese Clinical Trials Registration No. ChiCTR2300068781.