Atezolizumab + Bevacizumab + SBRT for Liver Cancer

Recruiting at 2 trial locations

Overseen By Jennifer Y Wo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must be taking: Anti-HBV therapy

Must not be taking: Anticoagulants, NSAIDs

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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: 7

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is evaluating the safety and tolerability of the drugs atezolizumab and bevacizumab with stereotactic body radiation therapy (SBRT) for treating unresectable hepatocellular carcinoma. This study involves the following interventions: * Atezolizumab * Bevacizumab * Stereotactic body radiation therapy (SBRT)

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there are certain restrictions on medications like full-dose anticoagulants and NSAIDs, and a washout period is required for some prior treatments. It's best to discuss your specific medications with the trial team.

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

Research shows that the combination of atezolizumab and bevacizumab is effective in increasing overall survival for patients with advanced liver cancer, and it has become a standard treatment option. This combination has been proven to be superior to other treatments like sorafenib for liver cancer that cannot be treated with surgery or other local methods. ^{1 2 3 4 5}

Is the combination of atezolizumab, bevacizumab, and SBRT 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 evaluated for varices (enlarged veins) before starting treatment. The safety of adding SBRT to this combination has not been specifically addressed in the available studies. ^{3 5 6 7 8}

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

This treatment combines two drugs, atezolizumab and bevacizumab, with stereotactic body radiation therapy (SBRT), offering a novel approach that may improve survival in liver cancer patients compared to traditional treatments like sorafenib. Atezolizumab helps the immune system attack cancer cells, bevacizumab blocks blood supply to tumors, and SBRT delivers precise radiation, potentially enhancing the overall effectiveness. ^{1 2 3 5 9}

Research Team

Jennifer Y Wo, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for adults with unresectable hepatocellular carcinoma (liver cancer), who have not had certain prior treatments, and whose liver function is relatively preserved (Child-Pugh A). They should have no more than 5 liver lesions, no severe portal hypertension or significant heart disease, and must not be pregnant or breastfeeding. Contraception use is required for participants of childbearing potential.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I have had TACE or DEB treatments with a 2-week break before this trial.

My liver is functioning well according to a recent test.

Exclusion Criteria

History of severe anaphylactic reactions to specific substances

My high blood pressure is not well controlled.

I do not have any unmanaged ongoing illnesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Safety lead-in phase to determine the maximum tolerated dose (MTD) of SBRT with atezolizumab and bevacizumab

18 weeks

6 cycles (1 visit per cycle)

Expanded Study

Participants receive Atezolizumab and Bevacizumab with SBRT, followed by Atezolizumab and Bevacizumab every cycle

Variable, based on safety and benefit

1 visit per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab
• Stereotactic body radiation therapy (SBRT)

Trial Overview The study tests the combination of atezolizumab and bevacizumab drugs with stereotactic body radiation therapy (SBRT) to see if it's safe and tolerable for treating liver cancer that can't be removed by surgery. Participants will receive these medications alongside targeted radiation treatment.

Participant Groups

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

Study will begin with a safety lead of 6 participants to determine the maximum tolerated dose (MTD) of Stereotactic beam radiation therapy (SBRT) with atezolizumab and bevacizumab followed by study expansion to 14 more participants after maximum tolerated dose (MTD) is established. Safety Lead-In: 6 cycles/18 weeks (study cycle is 3 weeks/21 days) * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-6: Atezolizumab + Bevacizumab (1x) every 3 weeks Expanded Study: * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-End:Atezolizumab + Bevacizumab (1x) every cycle

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

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]

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 study of 1447 patients treated with tyrosine-kinase inhibitors for hepatocellular carcinoma, only 29% were eligible for the combination therapy of atezolizumab-bevacizumab based on the IMbrave-150 trial criteria, indicating limited real-world applicability.

Eligible patients showed a median overall survival of 14.9 months, which was longer than non-eligible patients, suggesting that those who meet the criteria have better baseline health and cancer characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors. Stefanini, B., Bucci, L., Santi, V., 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 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-bevacizumab (atezo-bev) is effective as a first-line treatment for unresectable hepatocellular carcinoma (uHCC), showing a pooled overall survival of 13.8 months and a progression-free survival of 6.86 months across 5400 patients in 47 studies.

Patients with Child-Turcotte-Pugh (CTP) class B cirrhosis experienced similar objective response rates to those with CTP-A cirrhosis, but had shorter progression-free survival, indicating that atezo-bev is safe and effective for both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Kulkarni, AV., Tevethia, H., Kumar, K., et al.[2023]

In a study of 36 patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh B liver function, the combination of atezolizumab and bevacizumab (Ate/Bev) showed modest efficacy, with an objective response rate of 11.1% and a median overall survival of 7.7 months.

However, this treatment was associated with a higher incidence of severe adverse events (44.4% in Child-Pugh B patients) compared to those with Child-Pugh A (15.8%), highlighting the need for careful monitoring and management of side effects in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab in patients with child-Pugh B advanced hepatocellular carcinoma. Cheon, J., Kim, H., Kim, HS., et al.[2023]

In the Phase 3 IMbrave150 trial, atezolizumab combined with bevacizumab showed a similar safety profile to sorafenib in patients with unresectable hepatocellular carcinoma (HCC), regardless of whether they had hepatitis B or C infections.

The rates of viral reactivation were low and comparable between the two treatment groups, with no cases of hepatitis flare reported in patients treated with atezolizumab + bevacizumab, suggesting it is a safe option for patients with HCC and viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab. Hsu, C., Ducreux, M., Zhu, AX., et al.[2023]

References

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

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

2. 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]

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

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors. [2022]

5. 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]

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. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab in patients with child-Pugh B advanced hepatocellular carcinoma. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab. [2023]