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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Atezolizumab plus Bevacizumab for liver cancer?

Research shows that the combination of atezolizumab and bevacizumab is effective and safe for treating advanced liver cancer, improving overall survival compared to previous treatments. This combination is now a standard treatment option for advanced liver cancer. ^{1 2 3 4 5}

Is the combination of SBRT, Atezolizumab, and Bevacizumab safe for liver cancer treatment?

The combination of Atezolizumab and Bevacizumab has been shown to be generally safe for patients with advanced liver cancer, with common side effects including high blood pressure, fatigue, and protein in the urine. However, there is a higher risk of bleeding, and patients should be checked for varices (enlarged veins) before starting treatment. ^{1 2 6 7 8}

How is the treatment of SBRT, Atezolizumab, and Bevacizumab for liver cancer different from other treatments?

This treatment combines SBRT (a precise form of radiation therapy) with Atezolizumab and Bevacizumab, which are drugs that help the immune system fight cancer and block blood supply to tumors, respectively. This combination is unique because it integrates targeted radiation with immunotherapy and anti-angiogenic therapy, offering a novel approach for treating advanced liver cancer. ^{1 2 5 7 9}

What is the purpose of this trial?

This study is evaluating the safety and tolerability of neoadjuvant stereotactic body radiation therapy (SBRT) with atezolizumab and bevacizumab for treating resectable hepatocellular carcinoma. This study involves the following study interventions: * Atezolizumab * Bevacizumab * Stereotactic Beam Radiation Therapy (SBRT) * Surgery

Research Team

Jennifer Y Wo, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab: A Novel Breakthrough in Hepatocellular Carcinoma. [2022]

4. England 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. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Atezolizumab Plus Bevacizumab for the Treatment of Patients with Advanced Unresectable or Metastatic Hepatocellular Carcinoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Impact of older age in patients receiving atezolizumab and bevacizumab for hepatocellular carcinoma. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. [2023]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab. [2023]