SCT-I10A combined with a bevacizumab biosimilar (SCT510) versus sorafenib in the first-line treatment of advanced hepatocellular carcinoma: A randomized phase 3 trial.
Authors: Jianming Xu, Yanqiao Zhang, Gang Wang, Weiqing Chen, Li Zhuang, Shanzhi Gu, Jinfang Zheng, Lei Han, Zujiang Yu, Hongmei Sun, Xiaoyong Wei, Ying Cheng, Zheng Lu, Hailan Lin, Bo Zhu, Guicheng Wu, Kaijian Lei, Wenlin Gai, Liangzhi Xie
Journal: Journal of Clinical Oncology (2024)

4092 Background: Hepatocellular carcinoma (HCC) is a significant health concern in China, and it has been a leading cause of cancer-related deaths. Immunotherapy combined with anti-vascular growth therapy is the first recommended therapy. In this study, we evaluated the safety and efficacy of SCT-I10A (an anti-programmed death 1 [PD-1] monoclonal antibody) combined with SCT510 (a bevacizumab biosimilar) compared to sorafenib as the first-line treatment for advanced HCC. Methods: In this open-label, multicenter, phase 3 trial (NCT04560894) conducted in China, patients with advanced HCC who had not received prior system therapy were enrolled and randomly assigned (2:1) to receive SCT-I10A (200 mg every three weeks [Q3W]) plus SCT510 (a bevacizumab biosimilar, 15 mg/kg Q3W) or sorafenib (400 mg orally twice daily) until no clinical benefit or unacceptable toxicity. Randomization was stratified by ECOG performance status (0 vs. 1), baseline alpha-fetoprotein level (&lt;400ng/ml vs. ≥400ng/ml), macrovascular invasion or extrahepatic metastasis (yes vs. no). The co-primary endpoints were overall survival (OS) and progression-free survival (PFS) as assessed by the blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the full analysis set. Results: At the data cutoff for the interim analysis (November 2, 2023), a total of 346 patients were enrolled and received at least one dose (SCT-I10A plus SCT510 group, n=230; sorafenib group, n=116), and the median follow-up was 19.7 months. The SCT-I10A plus SCT510 group exhibited a significantly longer median OS than that in the sorafenib group (22.1 vs. 14.2 months, hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.44, 0.81; p=0.0008). Median PFS was prolonged significantly in the SCT-I10A plus SCT510 group compared to the sorafenib group (7.1 vs. 2.9 months; HR 0.50; 95%CI: 0.38, 0.65; p&lt;0.0001). The objective response rate (ORR) was higher in the SCT-I10A plus SCT510 group (32.8% [75/229]) than in the sorafenib group (4.3% [5/116]). Grade ≥3 treatment-related adverse events (TRAEs) were observed in 42.6% (98/230) of patients in the SCT-I10A plus SCT510 group and 33.6% (39/116) of patients in the sorafenib group. The most common grade ≥3 TRAE was hypertension (SCT-I10A plus SCT510 group vs. sorafenib group: 7.8% [18/230] vs. 4.3% [5/116]). Three drug-related deaths (unknown cause, hemorrhage intracranial, or upper gastrointestinal hemorrhage in 1 patient each) occurred and were related to SCT510. Conclusions: The combination of SCT-I10A and SCT510 showed substantial clinical advantages and an acceptable safety profile in patients with advanced HCC, thereby supporting its suitability as a first-line treatment option for HCC. Clinical trial information: NCT04560894 .