SBRT + Atezolizumab + Bevacizumab for Liver Cancer

Overseen By Jennifer Y Wo, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Must not be taking: Anticoagulants, NSAIDs, Immunosuppressants, others

Disqualifiers: Metastasis, Hypertension, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new treatment combination for surgically removable liver cancer. The treatment includes a precise radiation therapy called SBRT (Stereotactic Beam Radiation Therapy) and two drugs, atezolizumab (Tecentriq) and bevacizumab (Avastin). These drugs help the immune system fight cancer and inhibit the growth of blood vessels that feed tumors. Suitable participants are those diagnosed with hepatocellular carcinoma confined to the liver and eligible for surgical removal. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative combination.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like full-dose anticoagulants, high-dose aspirin, and systemic immunosuppressive drugs are restricted close to the start of the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that stereotactic body radiation therapy (SBRT) is generally safe and effective for liver cancer, such as hepatocellular carcinoma (HCC). It helps control tumors and is usually well-tolerated, meaning it doesn't cause severe side effects for most people.

The combination of two drugs, atezolizumab and bevacizumab, has also been studied for liver cancer. Studies suggest this treatment is safe for most patients and can improve survival rates. While all treatments can have side effects, serious problems are uncommon.

In summary, research indicates that SBRT, atezolizumab, and bevacizumab are generally safe for treating liver cancer like HCC, with most patients not experiencing severe side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining SBRT, atezolizumab, and bevacizumab for liver cancer because this approach is quite different from the standard treatments, like surgery or systemic chemotherapy. Atezolizumab is an immune checkpoint inhibitor that helps the body’s immune system target cancer cells more effectively. Bevacizumab works by cutting off the blood supply tumors need to grow. Stereotactic beam radiation therapy (SBRT) delivers high doses of radiation precisely to the tumor in just a few sessions, minimizing damage to surrounding tissue. This combination has the potential to enhance effectiveness while reducing side effects compared to traditional therapies, offering a new avenue for tackling liver cancer.

What evidence suggests that this trial's treatments could be effective for liver cancer?

This trial will evaluate the combination of stereotactic body radiation therapy (SBRT), atezolizumab, and bevacizumab for liver cancer. Research has shown that SBRT is effective for liver cancer, with one study finding it stopped the cancer from growing or spreading in 95% of cases. Additionally, the combination of atezolizumab and bevacizumab has proven effective for liver cancer that cannot be surgically removed, helping patients live longer and slowing the cancer's progression. Real-world evidence supports the promise of these treatments in managing liver cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Jennifer Y Wo, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with resectable hepatocellular carcinoma (a type of liver cancer) who have good liver function (Child-Pugh A), no history of certain bleeding events or severe allergies, and are not pregnant. They must be able to understand the study and consent to it, have measurable disease without vascular invasion, and agree to use contraception.

Inclusion Criteria

The number of certain white blood cells in your body, called neutrophils, must be at least 1,500 per microliter.

I have not received any treatment for my liver cancer lesion.

You have enough white blood cells in your body (at least 3,000/mcL).

Exclusion Criteria

Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies

Evidence of bleeding diathesis or significant coagulopathy

I have had lung conditions like pulmonary fibrosis or pneumonitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic beam radiation therapy (SBRT) on three treatment days arranged on an every-other-day basis

1 week

3 visits (in-person)

Treatment

Participants receive two 3-week cycles of atezolizumab and bevacizumab

6 weeks

Atezolizumab on day 1 of each cycle, Bevacizumab 1x weekly

Surgery

Surgery is performed 6-8 weeks after the last infusions of atezolizumab and bevacizumab

6-8 weeks post-treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Stereotactic Beam Radiation Therapy (SBRT)

Trial Overview The trial tests the combination of SBRT (a precise form of radiation therapy), Atezolizumab, Bevacizumab, followed by surgery in patients with resectable liver cancer. It aims to assess how safe this treatment sequence is and how well patients tolerate it.

How Is the Trial Designed?

Group I: Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab Experimental Treatment 3 Interventions

Participants will: * undergo a pre-treatment biopsy with fiducial marker placement * receive Stereotactic beam radiation therapy (SBRT) on three treatment days which will be arranged on an every-other-day basis * receive two 3-week (21 days) cycles of atezolizumab plus bevacizumab * receive Atezolizumab on day 1 for 2 study cycles. * receive Bevacizumab 1x weekly for 2 study cycles * Surgery after SBRT and the two cycles of atezolizumab and bevacizumab, unless participants are otherwise informed by their doctor. The planned surgery will take place 6-8 weeks after the last infusions of atezolizumab and bevacizumab.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

Atezolizumab in combination with bevacizumab has been approved by the FDA for treating unresectable hepatocellular carcinoma (HCC), showing improved overall survival (OS) and progression-free survival (PFS) compared to sorafenib, with a hazard ratio of 0.58 for OS.

The combination therapy resulted in a median PFS of 6.8 months versus 4.3 months for sorafenib, although it was associated with a higher incidence of hemorrhage (25% vs. 17%), highlighting the need for careful monitoring of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Atezolizumab Plus Bevacizumab for the Treatment of Patients with Advanced Unresectable or Metastatic Hepatocellular Carcinoma. Casak, SJ., Donoghue, M., Fashoyin-Aje, L., et al.[2022]

Atezolizumab combined with bevacizumab demonstrated good efficacy in treating advanced hepatocellular carcinoma (HCC), with a pooled overall response rate of 26% and a median overall survival of 14.7 months based on a review of 23 studies involving 3168 patients.

The treatment was well-tolerated, with 83% of patients experiencing any grade adverse events, and 30% experiencing grade 3 or higher adverse events, indicating that while side effects are common, the combination therapy remains a viable first-line option for advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab treatment for advanced hepatocellular carcinoma in the real world: a single-arm meta-analysis. Gao, X., Zhao, R., Ma, H., et al.[2023]

In a multicenter study of 121 patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev), the objective response rate was 24% and the disease control rate was 76%, demonstrating real-world efficacy similar to phase III trial results.

The most common severe side effect was an increase in aspartate aminotransferase levels (10.7%), and factors like elevated baseline neutrophil-to-lymphocyte ratio were linked to poorer progression-free and overall survival, indicating the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. Cheon, J., Yoo, C., Hong, JY., et al.[2022]

In a multicenter study involving 30 patients with unresectable hepatocellular carcinoma and extrahepatic portal vein tumor thrombus, the combination of intensity-modulated radiotherapy (IMRT) with systemic atezolizumab and bevacizumab (atezo/bev) resulted in a high objective response rate of 76.6% and a median overall survival of 9.8 months.

The treatment was found to have an acceptable safety profile, with neutropenia being the most common adverse event, and no treatment-related deaths reported, suggesting that this combination therapy could be a promising option for patients with this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study. Wang, K., Xiang, YJ., Yu, HM., et al.[2023]

Atezolizumab plus bevacizumab significantly improves progression-free survival (PFS) compared to lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC), based on a meta-analysis of 8 studies involving 3690 patients.

Patients receiving atezolizumab plus bevacizumab experience fewer severe adverse events (grade 3/4) compared to those treated with lenvatinib, indicating a better safety profile, although lenvatinib may be more effective for overall survival in non-viral patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Liu, J., Yang, L., Wei, S., et al.[2023]

Atezolizumab plus bevacizumab therapy shows promising efficacy for advanced hepatocellular carcinoma (HCC), achieving an objective response rate of 15.6% and a high disease control rate of 93.8% among 34 patients, regardless of liver function or treatment line.

Following the failure of atezolizumab plus bevacizumab therapy, lenvatinib treatment can also be effective, but careful monitoring of liver function is necessary, as indicated by significant reductions in liver function scores in patients receiving lenvatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma. Komatsu, S., Yano, Y., Fujishima, Y., et al.[2022]

In a study of 191 patients with unresectable hepatocellular carcinoma (HCC), the combination therapy of atezolizumab and bevacizumab showed similar overall survival and progression-free survival rates in older patients (≥65 years) compared to younger patients (<65 years), indicating its efficacy across age groups.

The safety profile of the combination therapy was comparable between older and younger patients, with similar rates of treatment-related adverse events, including severe adverse events, suggesting that older patients can tolerate this treatment as well as younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. Vithayathil, M., D'Alessio, A., Fulgenzi, CAM., et al.[2023]

In a study of seven patients with advanced hepatocellular carcinoma (HCC) receiving atezolizumab and bevacizumab, the addition of radiotherapy (RT) was found to be feasible, with no severe hematologic adverse events reported.

Despite the addition of RT, disease progression occurred in 85.7% of patients, indicating that while RT may be safe, its effectiveness in improving progression-free survival (PFS) and overall survival (OS) remains uncertain and requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Kim, TH., Kim, BH., Cho, YR., et al.[2023]

The combination of atezolizumab and bevacizumab has been shown to significantly increase overall survival in patients with advanced hepatocellular carcinoma (HCC) compared to sorafenib.

The FDA's approval of this combination therapy marks a significant advancement in the treatment of HCC, potentially changing how the disease is managed across all stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab: A Novel Breakthrough in Hepatocellular Carcinoma. Castet, F., Willoughby, CE., Haber, PK., et al.[2022]

Citations

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Real‐World Outcomes of Atezolizumab–Bevacizumab in ... Real‐world data from the CHIEF cohort demonstrate AtezoBev's effectiveness in a large French HCC population, showing survival and response rates ...

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Efficacy of atezolizumab plus bevacizumab for ... This study provides real-world evidence supporting the long-term efficacy of atezolizumab plus bevacizumab (A+B) for unresectable hepatocellular carcinoma, ...

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Atezolizumab plus Bevacizumab in Unresectable ... In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival ...

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How TECENTRIQ + Avastin ® (bevacizumab) May Help TECENTRIQ + Avastin was more effective in treating HCC than sorafenib. More patients LIVED LONGER and HAD A LOWER CHANCE of tumors growing or spreading ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00645

Clinical Outcomes and Histologic Findings of Patients With ... The median progression-free survival was 23.2 months for patients with durable PR and 13.2 months for those with durable SD. In the real-world ...

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Safety and Efficacy of Atezolizumab/Bevacizumab in Patients ... We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction.

7. tecentriq-hcp.com tecentriq-hcp.com/hcc.html

First Line Treatment for Unresectable or Metastatic HCC Important Safety Information · Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. There are no available ...

8. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14400-9

Safety and efficacy of atezolizumab/bevacizumab in ... We conclude that the combination of atezolizumab and bevacizumab is a safe and effective option for patients with unresectable hepatocellular carcinoma ...