Abstract CT171: Cadonilimab in combination with lenvatinib and stereotactic body radiotherapy in potentially resectable hepatocellular carcinoma (UniRTX): A single-arm, phase II clinical trial

Abstract Background: Hepatocellular Carcinoma (HCC) has a high incidence and mortality rate in China, with half of the cases initially diagnosed as advanced stage. Following conversion treatment, a growing number of patients previously classified unresectable may be converted to resectable status. This trial evaluated the efficacy and safety of Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) in combination with lenvatinib and stereotactic body radiotherapy (SBRT) for patients with potentially resectable HCC. Methods: This single-arm, single center, phase II study will enroll 27 treatment-naive patients confirmed potentially resectable HCC (technically unresectable in stage Ia-IIa and resectable in stage IIb-IIIa), based on China liver cancer staging. The participants underwent SBRT(18-40 Gy/3-5F) once, followed by Cadonilimab (10mg/kg, IV, Q3W) and lenvatinib (8mg, PO, QD) for 4 cycles. The primary endpoints are overall response rate (ORR) according to criteria in solid tumors (RECIST) version 1.1 and mRECIST. Secondary endpoints included surgical conversion rate, major pathological response (MPR, defined as >70% necrosis of the resected tumor), disease control rate (DCR), progression-free survival (PFS), overall survival(OS) and safety. Results: From April 18, 2023, a total of 22 patients were enrolled, with at least one radiographic evaluation conducted for 19 patients. The mean age was 54 years, and 73.7% of patients were diagnosed with BCLC-C stage . Among them, 13 (68.4%) had an alpha-fetoprotein level ≥400 ng/ml and tumor nodules ≥4 accounted for 36.8%. Out of the evaluated patients, partial response was observed in 17 cases while stable disease was noted in one case. The ORR was 89.5%, and the DCR was 94.7%. Hepatectomy/ablation was optional, with eight patients opting for surgical or ablation. Two patients met the criteria for surgery but declined, and four patients are currently undergoing therapy. Notably, three patients exhibited MPR, while three achieved complete pathological response (pCR) upon postoperative pathologic evaluation. The safety analysis set comprised 22 patients. The most common treatment-related adverse events (TRAEs) of any grade were hypertension (54.6%), abdominal distension (54.6%), White blood cell decreased (36.4%), and ALT/AST increased (36.4%). Only one patient had grade 3 TRAE, which is duodenal ulcer. Conclusions: Cadonilimab in combination with Lenvatinib and Stereotactic Body Radiotherapy has demonstrated promising antitumor efficacy and a favorable safety profile in potentially resectable HCC. Moreover, this therapeutic approach is anticipated to enhance the rate of liver resection in these patients. Clinical trial information: ChiCTR2300068781. Citation Format: Jun Xue, Jing Tang, Dongen Liu, Hongli Liu, Zhenyu Lin, Xiong Cai, Qinggang Hu, Bicheng Wang, Shiran Sun, Chidan Wan, Tao Zhang. Cadonilimab in combination with lenvatinib and stereotactic body radiotherapy in potentially resectable hepatocellular carcinoma (UniRTX): A single-arm, phase II clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT171.