Abstract CT211: Safety of prompt initiation of durvalumab or STRIDE (single tremelimumab regular interval durvalumab) regimen as hepatocellular carcinoma (HCC) treatment for patients with chronic active hepatitis B
Authors: Shao Yu-Yun , Chen Ching-Tso , Wu Tsung-Che , Liu Tsung-Hao , Chuang Chien-Huai , Cheng Ann-Lii , Hsu Chih-Hung 
Published: April 2024

Abstract
Background: Chronic hepatitis B is an etiology of HCC. Clinical trials using immune checkpoint inhibitors (ICIs) as HCC treatment typically exclude patients with chronic active hepatitis B (serum hepatitis B virus [HBV] viral load &gt; 2000 IU/mL) or require the HBV viral load to be below a certain level using anti-HBV medications. In the phase 3 HIMALAYA study, the STRIDE regimen was superior to sorafenib and durvalumab was noninferior to sorafenib in overall survival benefits. This study explored the safety of concurrent administration of STRIDE or durvalumab with anti-HBV mediations for patients with chronic, active hepatitis B infection.
Methods: We enrolled patients with advanced HCC, Child-Pugh A liver function reserve, and chronic active hepatitis B not under anti-HBV treatment. Initially, only patients naïve to ICIs were eligible, and patients received durvalumab 1500mg iv every 4 weeks until disease progression, occurrence of unacceptable toxicities, or the maximum treatment duration of 2 years. After the positive results of the HIMALAYA study, we added tremelimumab 300mg iv on D1 following the STRIDE regimen and allowed enrollment of patients who had received prior programmed cell death-1 blockade therapy. Patients initiated entecavir as HBV treatment within 7 days of starting ICI therapy. The plan was to enroll 30 patients, with the primary outcome of HBV reactivation (a ≥2 log increase in serum HBV DNA compared to the baseline level).
Results: The study is still ongoing and as of 31 Aug 2023, 19 patients were enrolled. Two patients were female, and the median age was 65.5 years. Ten patients received durvalumab alone, and 9 received the STRIDE regimen. The ALBI grade was 1 and 2 in 3 (16%) and 16 (84%) patients, respectively. Macrovascular invasion and extrahepatic spread were present in 11 (58%) and 11 (58%) patients, respectively; 12 (63%) patients had alpha-fetoprotein level ≥ 400 ng/mL. Eleven (58%) patients had received prior systemic therapy for HCC, such as sorafenib (n = 9), lenvatinib (n = 5), and regorafenib (n = 4). The mean±standard deviation baseline HBV viral load was 1.18±0.44 mIU/mL. With the median follow-up on 6.1 months, no patients experienced HBV reactivation or HBV-associated hepatitis. Hepatitis flare (ALT increase to ≥3 times the baseline level) was noted in 4 (21%) patients, but none were considered HBV-associated. The best objective tumor response was complete and partial response in 0 and 5 (26.3%) patients, respectively, and the disease control rate was 63.2%.
Conclusion: In the preliminary results, simultaneous initiation of immunotherapy and anti-HBV medications in patients with HCC and chronic active hepatitis B did not increase HBV reactivation rate. This study was supported by AstraZeneca (NCT04294498).
Citation Format: Yu-Yun Shao, Ching-Tso Chen, Tsung-Che Wu, Tsung-Hao Liu, Chien-Huai Chuang, Ann-Lii Cheng, Chih-Hung Hsu. Safety of prompt initiation of durvalumab or STRIDE (single tremelimumab regular interval durvalumab) regimen as hepatocellular carcinoma (HCC) treatment for patients with chronic active hepatitis B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT211.