Atezolizumab and Bevacizumab With Photon Radiotherapy for Unresectable Hepatocellular Carcinoma

Investigation of Antitumor Immune Response in Patients With Unresectable Hepatocellular Carcinoma Undergoing Photon Radiotherapy Combined With Atezolizumab and Bevacizumab

Atezolizumab and Bevacizumab With Photon Radiotherapy for Unresectable Hepatocellular Carcinoma (NCT06339424) is a Phase 2 interventional studying Hepatocellular Carcinoma, sponsored by Chang Gung Memorial Hospital. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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 highly efficacious in controlling localized solid tumors and has become an integral component of the treatment algorithm for unresectable HCC. Importantly, a recent retrospective cohort described that RT combined with atezolizumab plus bevacizumab was associated with favorable median overall survival of 16.1 months (Manzar et al, Cancers 2022). Our preclinical study (Hsieh et al., Science Immunology 2022) revealed that RT combined with PD-L1/PD-1 blockade induces immunogenic cell death and tumor antigen cross-presentation in antigen-presenting cells, thereby potentiating the systemic antitumor T cell responses in murine tumor models. However, whether the combinatorial therapy with RT, atezolizumab, and bevacizumab can trigger synergistic antitumor effects and systemic immune mobilization has not yet been validated in clinical trials for unresectable HCC. Both atezolizumab/bevacizumab and X-ray RT are approved treatment methods for unresectable HCC by the U.S. and Taiwan Food and Drug Administration (FDA). The present phase II non-randomized trial aims to prospectively document the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with atezolizumab/bevacizumab combined with conventional photon radiotherapy.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Hepatocellular Carcinoma and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 45 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Participants must have a diagnosis of HCC that is deemed unsuitable for surgical resection or transplant. Participants may have multiple lesions with a total maximal tumor dimension of \< 20 cm, and no one lesion \> 15 cm. Diagnosis should be confirmed by at least 1 criterion listed below: - Histologically or cytologically proven diagnosis of HCC. - Typical arterial enhancement and delayed washout on multiphasic CT or MRI. 2. Age ≥18 years at the time of signing the willing to sign a consent form document. 3. You should be able to carry out daily activities with 0 level of ability (ECOG 0)-1. 4. Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C). 5. Child-Pugh score 5-6 liver function within 28 days of study registration. 6. Documented virology status of hepatitis B virus (HBV), as confirmed by screening HBV serology test. 7. Documented virology status of hepatitis C virus (HCV), as confirmed by screening HCV serology test. 8. Ability to understand and the willingness to sign a written willing to sign a consent form document 9. Adequate bone marrow, liver, and renal function within 4 weeks before study registration - blood count (hemoglobin) at least 9.0 g/dL - Absolute neutrophil count (ANC) ≥ 1,000/mm3 - Platelet count ≥ 50,000/μL - Total bilirubin \< 2.5 mg/dL - Serum albumin \>2.8 g/dL - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) - Prothrombin time ≤ 6 seconds prolonged - Serum creatinine ≤ 1.5 mg/dL Who Should NOT Join This Trial: 1. Prior invasive malignancy unless disease-free for a minimum of 2 years 2. Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields 3. Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time 4. Untreated active hepatitis B or hepatitis C 5. Moderate to severe or intractable ascites ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Participants must have a diagnosis of HCC that is deemed unsuitable for surgical resection or transplant. Participants may have multiple lesions with a total maximal tumor dimension of \< 20 cm, and no one lesion \> 15 cm. Diagnosis should be confirmed by at least 1 criterion listed below: * Histologically or cytologically proven diagnosis of HCC. * Typical arterial enhancement and delayed washout on multiphasic CT or MRI. 2. Age ≥18 years at the time of signing the informed consent document. 3. ECOG performance status 0-1. 4. Barcelona Clinic Liver Cancer (BCLC) stages Intermediate (B) or Advanced (C). 5. Child-Pugh score 5-6 liver function within 28 days of study registration. 6. Documented virology status of hepatitis B virus (HBV), as confirmed by screening HBV serology test. 7. Documented virology status of hepatitis C virus (HCV), as confirmed by screening HCV serology test. 8. Ability to understand and the willingness to sign a written informed consent document 9. Adequate bone marrow, liver, and renal function within 4 weeks before study registration * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥ 1,000/mm3 * Platelet count ≥ 50,000/μL * Total bilirubin \< 2.5 mg/dL * Serum albumin \>2.8 g/dL * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) * Prothrombin time ≤ 6 seconds prolonged * Serum creatinine ≤ 1.5 mg/dL Exclusion Criteria: 1. Prior invasive malignancy unless disease-free for a minimum of 2 years 2. Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields 3. Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time 4. Untreated active hepatitis B or hepatitis C 5. Moderate to severe or intractable ascites 6. Presence of distant metastases that cannot be encompassed by photon radiotherapy 7. Untreated or incompletely treated esophageal or gastric varices 8. Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration * Myocardial infarction within the last 6 months prior to study entry * Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry * A bleeding episode within 6 months prior to study entry due to any cause. * Thrombolytic therapy within 28 days prior to study entry. * Known bleeding or clotting disorder. * Uncontrolled psychotic disorder 9. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception 10. Prior solid organ transplantation. 11. Prior or active autoimmune disease (AID) including autoimmune hepatitis, inflammatory bowel disease, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, and multiple sclerosis. 12. Prior or active thrombotic or bleeding disorders, hemoptysis, cerebral vascular accident, significant cardiac disease (ischemic or congestive heart failure), or gastrointestinal perforation. 13. Inability to treat all sites of disease by photon radiotherapy (such as extrahepatic metastases or massive liver tumors whereby the liver constraints cannot be met for covering all sites of liver tumors.) 14. Known HIV infection.

Treatments Being Tested

DRUG

Atezolizumab

Atezolizumab 1200 mg will be administered as an IV infusion on Day 1 of each cycle, with cycles occurring every 3 weeks. The initial dose will be delivered over 60 (± 15) minutes, and if well-tolerated, subsequent infusions may be given over 30 minutes. For patients who achieve a complete response (CR) within one year of treatment, atezolizumab should be continuously used for a year. For patients who experience a partial response (PR), atezolizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive atezolizumab for 6 months. In the case of PD, atezolizumab should be discontinued at the time when PD is confirmed.

DRUG

Bevacizumab

Bevacizumab 15 mg/kg will be administered as an IV infusion on Day 1 of each 3-week cycle. The initial dose will be delivered over 90 minutes (±15 minutes), and if well-tolerated, subsequent infusions may be given over 60 minutes. For patients who achieve a complete response (CR) within one year of treatment, bevacizumab should be continuously used for a year. In the case of patients experiencing a partial response (PR), bevacizumab should be continued until achieving CR or experiencing progressive disease (PD). Patients with stable disease should receive bevacizumab for 6 months. In the event of PD, bevacizumab should be discontinued when PD is confirmed. Temporary withholding or dose reduction of bevacizumab is permitted if patients experience adverse events such as bleeding episodes, severe hypertension, or proteinuria at the discretion of the treating physician.

RADIATION

Photon radiotherapy

* 39.6-72.6 Gy in 22 fractions for tumors ≤1 cm from the hepatic hilum, bowel, and heart. * 30-66 Gy in 10 fractions for tumors \>1 cm from the hepatic hilum, bowel, and heart. * 27.5-50 Gy in 5 fractions using stereotactic body radiation therapy (SBRT) techniques

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Chang Gung Memorial Hospital at Linkou

Taoyuan City, Taiwan, Taiwan

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06339424), the sponsor (Chang Gung Memorial Hospital), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06339424 clinical trial studying?

Who can participate in NCT06339424?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06339424?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06339424. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06339424. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.