Prompt initiation of durvalumab and tremelimumab treatment for unresectable hepatocellular carcinoma in patients with chronic active hepatitis B.

568 Background: Chronic hepatitis B virus (HBV) infection is a common etiology of HCC, especially in East Asia. Clinical trials using immune checkpoint inhibitors (ICIs) usually exclude patients with chronic active hepatitis B (serum HBV viral load > 2000 IU/mL) or require the HBV viral load to be below a certain level using anti-HBV medications. This study examines the safety and efficacy of concurrently administering the STRIDE regimen (durvalumab with a single dose of tremelimumab) or durvalumab alone with anti-HBV medications in this patient population. Methods: We enrolled patients with advanced HCC, Child-Pugh A liver function reserve, and untreated chronic active hepatitis B. Initially, only patients naïve to ICIs were eligible, and patients received 1500mg of durvalumab intravenously every four weeks for up to two years except for disease progression or occurrence of unacceptable toxicities. After the positive results of the HIMALAYA study, we shifted to the STRIDE (single tremelimumab regular interval durvalumab) regimen, adding one dose of 300mg tremelimumab on the first day to regular durvalumab treatment, and allowed patients who had received prior programmed cell death-1 blockade therapy to be enrolled. Anti-HBV treatment with entecavir was initiated within seven days before starting ICI therapy. The primary endpoint was the rate of HBV reactivation (defined as a ≥2 log increase in serum HBV DNA from baseline) during the first six months. Results: Following the protocol design, 30 patients were enrolled. Two patients were female, and the mean age was 66.9 years. Ten patients received durvalumab alone, and 20 received the STRIDE regimen. Macrovascular invasion and extrahepatic spread were present in 16 (53.3%) and 20 (66.7%) patients, respectively; 18 (60%) patients had alpha-fetoprotein level ≥ 400 ng/mL. More than half (60.0%) of the patients had received prior systemic therapy for HCC, including 2 patients who had received PD-1 blockade therapy. Seven patients received the study treatment as the 3 rd or later line of systemic therapy. The mean±standard deviation baseline HBV viral load was 771.0±354.1 KIU/mL. No patients experienced HBV reactivation or HBV-associated hepatitis. Hepatitis flare was noted in 8 (26.7%) patients, but none of them were associated with HBV reactivation. The objective tumor response rate was 10% and 25% for the durvalumab treatment alone and the STRIDE regimen, respectively. No unexpected toxicities were identified in this study. The most common treatment-related adverse events were skin rash and liver function test abnormalities. Conclusions: For patients with chronic active hepatitis B, ICI therapy could be promptly initiated as long as anti-HBV medications were administered simultaneously. This study was partially supported by AstraZeneca. Clinical trial information: NCT04294498 .