Tremelimumab plus durvalumab (the STRIDE regimen) is an approved first-line therapy for unresectable hepatocellular carcinoma (HCC); however, it demonstrates limited efficacy, with an objective response rate (ORR) of only 20.1%. Radiation therapy (RT) is highly effective in controlling localized solid tumors and has become an integral component of the treatment algorithm for unresectable HCC. Preclinical studies have shown that combining RT with PD-L1/PD-1 blockade promotes immunogenic cell death and enhances antigen presentation by dendritic cells, thereby boosting systemic T cell-mediated antitumor responses in mouse models. The addition of CTLA-4 inhibition further enhances antigen cross-priming following RT. Recent retrospective data also indicate that combining RT with immune-oncology agents is associated with improved overall survival and prolonged time to progression compared to RT or immunotherapy alone. However, the clinical benefit and immunologic impact of combining RT with tremelimumab and durvalumab have not yet been evaluated in prospective clinical trials for unresectable HCC. This phase II, single-arm clinical trial aims to assess the safety, efficacy, and immunologic effects of combining proton RT with tremelimumab and durvalumab in patients with unresectable HCC.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
* 39.6-72.6 Gy in 22 fractions for tumors ≤1 cm from hepatic hilum, bowel, and heart. * 30-66 Gy in 10 fractions for tumors \>1 cm from hepatic hilum, bowel, and heart. * 27.5-50 Gy in 5 fractions using stereotactic body radiation therapy (SBRT) techniques
Tremelimumab 300 mg will be administered as an IV infusion for one dose
Treatment Duration Guidelines: \* Complete Response (CR): Patients who achieve a CR within one year of treatment will continue durvalumab for a total duration of two years. \* Partial Response (PR): Patients who achieve a PR should continue durvalumab until achieving CR, disease progression (PD), or for a total duration of two years. \* Stable Disease (SD): Patients with SD will receive duvalumab for a total of 6 doses.
Chang Gung Memorial Hospital at Linkou
Taoyuan City, Taiwan, Taiwan
RECRUITINGProgression free survival
Progression free survival is defined as the time from signing the informed consent to the first occurrence of disease progression or death from any cause (whichever occurs first) according to RECIST1.1
Time frame: 12 months
Local control
Local control is defined as the time from signing the informed consent to the first occurrence of disease progression in the irradiated field according to RECIST1.1
Time frame: 12 months
Time to progression
Time to progression is defined as the time from signing the informed consent to the first occurrence of disease progression according to RECIST1.1
Time frame: 12 months
Overall Response Rate
Overall Response Rate is defined as a complete or partial response according to RECIST1.1
Time frame: 12 months
Overall survival
Overall survival is defined as the time from signing the informed consent to death from any cause.
Time frame: 12 months
Incidence and severity of adverse events
Description: Adverse events will be graded using CTCAE v5
Time frame: 12 months
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