The combination of serplulimab (Hansizhuang) with bevacizumab biosimilar HLX04 has demonstrated a manageable safety profile as first-line treatment for advanced hepatocellular carcinoma (HCC), according to new phase 2 trial results published in Cancer Immunology, Immunotherapy.
Safety Profile and Adverse Events
Among the 61 patients evaluated for safety, treatment-emergent adverse events (TEAEs) were observed in 98.4% of participants. Grade 3 or higher TEAEs affected 47.5% of patients, while serious TEAEs occurred in 27.9%. Three patients (4.9%) experienced grade 5 TEAEs, including one death attributed to hepatic failure and disease progression potentially linked to treatment.
The most frequently reported adverse events included elevated aspartate aminotransferase (49.2%), decreased platelet counts (49.2%), and proteinuria (44.3%). Several TEAEs led to treatment discontinuation, including individual cases of arrhythmia, increased blood bilirubin, gastrointestinal hemorrhage, intracranial hemorrhage, immune-mediated myocarditis, and proteinuria.
Trial Design and Patient Characteristics
The study enrolled 61 patients between September 2019 and April 2021, following the screening of 238 candidates. Treatment consisted of 3 mg/kg intravenous serplulimab combined with 10 mg/kg HLX04 administered every two weeks, with a treatment duration of up to two years.
The patient population was predominantly male (88.5%) with a median age of 55 years. Most participants (98.4%) had hepatitis B infections and Barcelona Clinic Liver Cancer stage C disease (82.0%). All patients were classified as Child-Pugh class A.
Efficacy Outcomes
The combination therapy showed promising efficacy results among 58 evaluable patients. The objective response rate as assessed by independent radiological review committee was 29.3% (95% CI, 18.1%-42.7%). The median progression-free survival reached 7.3 months, with 6- and 12-month rates of 51.3% and 27.6%, respectively.
Notably, the median overall survival was 20.4 months, with impressive 6- and 12-month survival rates of 93.1% and 74.1%, respectively. These results suggest significant potential for the combination therapy in treating advanced HCC.
Dr. Zhenggang Ren, Director of Hepatic Oncology at Zhongshan Hospital, Fudan University in Shanghai, emphasized the significance of these findings: "This study demonstrated that serplulimab combined with HLX04 was well tolerated in patients with advanced HCC in the first-line setting. The combination's promising antitumor activity and potential to prolong survival support further investigations for first-line treatment of HCC."
