NCT06133062: ProtonAB

Atezolizumab and Bevacizumab With Proton Radiotherapy for Unresectable Hepatocellular Carcinoma

Recruiting now Phase 2 Last updated 20 March 2026

What this trial tests

Phase 2 trial testing Atezolizumab in Hepatocellular Carcinoma Non-resectable in 45 participants. Currently enrolling.

Timeline

16 November 2023

Primary endpoint
30 September 2028

30 September 2030

Quick facts

Lead sponsor	Chang Gung Memorial Hospital
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	45
Start date	16 November 2023
Primary completion	30 September 2028
Estimated completion	30 September 2030
Sites	1 location across Taiwan

Drugs / interventions tested

• Atezolizumab (atezolizumab) — full drug profile →
• Bevacizumab (Bevacizumab-Bvzr) — full drug profile →
• Proton radiotherapy

Conditions studied

• Hepatocellular Carcinoma Non-resectable — all drugs for Hepatocellular Carcinoma Non-resectable →

Sponsor

Chang Gung Memorial Hospital

Who can join

18 and older, any sex, with Hepatocellular Carcinoma Non-resectable. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) in conjunction with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) has become the established standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). Despite an improved objective response rate (ORR) of 27%, the majority of patients face HCC progression and liver failure \[Finn et al., N Engl J Med 2020\]. Developing a new combined treatment strategy to overcome resistance to anti-PD-L1 and anti-VEGF is essential to improve patient outcomes.

Radiation treatment (RT) is notably effective in managing localized solid tumors and is a fundamental component of unresectable HCC treatment. Recent retrospective cohorts have demonstrated that proton RT targeting all hepatic tumors, along with PD-L1/programmed death-1 (PD-1) blockade, enhances ORR and progression-free survival for unresectable HCC patients, displaying a favorable safety profile (Su et al., Am J Cancer Res. 2022). Our preclinical study (Hsieh et al., Sci Immunol 2022) showcased that RT combined with PD-L1/PD-1 blockade stimulates immunogenic cell death and antigen cross-presentation in murine tumor models, promoting systemic antitumor T cell responses. Nonetheless, it is crucial to verify whether the combined therapy of proton RT, atezolizumab, and bevacizumab triggers synergistic antitumor effects and systemic immune activation in clinical trials for unresectable HCC. This phase II non-randomized trial aims to prospectively evaluate therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with atezolizumab/bevacizumab combined with proton radiotherapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immunotherapy in liver cancer: overcoming the tolerogenic liver microenvironment.
   Liu Y, Yang H, Li T, Zhang N. · · 2024 · cited 23× · PMID 39295859 · DOI 10.3389/fimmu.2024.1460282
2. Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot.
   Han Y, Tian X, Zhai J, Zhang Z. · · 2024 · cited 20× · PMID 38774648 · DOI 10.3389/fcell.2024.1363121
3. Immunological Effects of Proton Radiotherapy: New Opportunities and Challenges in Cancer Therapy.
   Zhang A, Fan L, Liu Q, Zuo X, et al · · 2025 · cited 5× · PMID 40061827 · DOI 10.1002/cai2.70003
4. Immunotherapy and Radiation Therapy Combinatorial Approaches in Hepatocellular Carcinoma.
   Tojjari A, Yu J, Saeed A. · · 2024 · cited 5× · PMID 38473415 · DOI 10.3390/cancers16051058
5. Combination of radiotherapy and ICIs in advanced hepatocellular carcinoma: A systematic review of current evidence and future prospects (Review).
   Ma C, Yu X, Zhang X, Su L, et al · · 2025 · cited 4× · PMID 40438865 · DOI 10.3892/ol.2025.15088
6. Efficacy and safety of the immune checkpoint inhibitor-radiotherapy combination in advanced/unresectable hepatocellular carcinoma: A systematic review and meta-analysis.
   Cui R, Yu X, Jiang Y, Li X. · · 2025 · cited 2× · PMID 40776902 · DOI 10.3892/ol.2025.15206
7. The Spatiotemporal Heterogeneity of Tumor-Associated Stromal Cells: Reprogramming Plasticity to Unlock Precision Cancer Immunotherapy.
   Lv Y, Duan T, Song J, Liu S, et al · · 2026 · cited 1× · PMID 41625480 · DOI 10.34133/cancomm.0002
8. Proton Radiotherapy Alone versus Combined with Immunotherapies or Tyrosine Kinase Inhibitors for Barcelona Clinic Liver Cancer Stage B or C Hepatocellular Carcinoma.
   Hsieh RC, Chen WP, Lee JC, Lin CH, et al · · 2025 · PMID 41585427 · DOI 10.1159/000550067