Atezolizumab + Bevacizumab for Liver Cancer

Overseen By Shondra Word

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Aspirin, Clopidogrel, NSAIDs, others

Disqualifiers: Autoimmune disease, Cardiovascular disease, Hypertension, 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)

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, atezolizumab (an immunotherapy drug) and bevacizumab (an anti-angiogenesis drug), to assist people with liver cancer who qualify for a liver transplant. The goal is to determine if these treatments can safely prepare patients for a transplant without increasing the risk of rejection within a year. This trial may suit those with liver cancer that cannot be surgically removed and who are eligible for a liver transplant. Participants will also receive a standard treatment called transarterial chemoembolization (TACE) every three months. As a Phase 4 trial, this research aims to understand how these already FDA-approved and effective treatments can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like high-dose aspirin, clopidogrel, and some anticoagulants are restricted. It's best to discuss your specific medications with the trial team.

What is the safety track record for atezolizumab and bevacizumab?

Research has shown that the combination of atezolizumab and bevacizumab is generally safe for people with liver cancer. Studies have found that this treatment can extend patients' lives and is usually well-tolerated. Most people experience manageable side effects. Reports often state that this combination does not cause serious health problems. It has been used successfully in patients whose liver cancer cannot be removed by surgery. Additionally, the FDA has already approved this treatment for similar conditions, indicating a known safety record. Overall, current evidence supports the safety of atezolizumab and bevacizumab for liver cancer patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using atezolizumab and bevacizumab for liver cancer because these drugs offer a promising new approach by combining the power of immunotherapy and anti-angiogenesis. Atezolizumab is an immune checkpoint inhibitor that helps the body's immune system recognize and attack cancer cells more effectively. Bevacizumab, on the other hand, works by restricting the blood supply that tumors need to grow, making this combination unique compared to traditional chemotherapy treatments. Together, they target the cancer in a way that existing options, like sorafenib or lenvatinib, do not, potentially leading to better outcomes for patients.

What is the effectiveness track record for atezolizumab and bevacizumab in treating liver cancer?

Research has shown that the combination of atezolizumab and bevacizumab, which participants in this trial will receive, effectively treats liver cancer, specifically hepatocellular carcinoma (HCC). Studies have found that this combination helps patients live longer and slows tumor growth compared to treatments like sorafenib. In real-world settings, 65% of patients remain alive after 12 months. This treatment often causes the tumor to partially shrink and the disease to remain stable, meaning the cancer does not worsen. For those with HCC that cannot be surgically removed, this combination has improved both overall survival and the time patients live without the cancer worsening. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adults with advanced liver cancer (HCC) outside Milan Criteria, eligible for a TACE procedure and liver transplant. They must have a life expectancy of at least 6 months, adequate organ function, no severe allergies to trial drugs or their components, and agree to use effective contraception. Excluded are those with recent significant cardiovascular issues, uncontrolled hypertension or bleeding disorders, certain infections like HIV or hepatitis B/C, other cancers within the last 5 years, previous HCC treatments before enrollment.

Inclusion Criteria

You are expected to live for at least 6 more months.

I am eligible for a liver transplant.

I have been tested for hepatitis B and either do not have it or it is not active.

Exclusion Criteria

I haven't had any cancer except skin cancer in the last 5 years.

I am currently on medication for hepatitis B.

I have a history of neurological issues, like seizures, not caused by cancer but treated with medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant/downstaging treatment with atezolizumab and bevacizumab for 6 months, along with standard of care transarterial chemoembolization (TACE) every 3 months, up to 4 treatments.

6 months

Regular visits for TACE and drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and tumor biomarker measurements.

1 year after liver transplant

Regular follow-up visits for biomarker assessments and monitoring

Extension

Participants may continue to be monitored for long-term outcomes such as recurrence-free survival and overall survival.

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab

Trial Overview The trial tests if combining Atezolizumab and Bevacizumab with standard transarterial chemoembolization (TACE) can help patients with hepatocellular carcinoma beyond Milan Criteria safely reach liver transplantation without increasing post-transplant rejection risk.

How Is the Trial Designed?

Group I: Atezolizumab + Bevacizumab Experimental Treatment 2 Interventions

Patients will receive transarterial chemoembolization (TACE) every 3 months, with a maximum of 4 treatments, plus atezolizumab combined with 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?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

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

In the phase 3 IMbrave050 study involving 668 patients with high-risk hepatocellular carcinoma, adjuvant treatment with atezolizumab plus bevacizumab significantly improved recurrence-free survival compared to active surveillance, indicating its potential efficacy as a post-surgery treatment.

However, the treatment was associated with a higher incidence of severe adverse events (41% of patients) compared to the active surveillance group (13%), highlighting the need for careful consideration of the benefit-risk profile in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial. Qin, S., Chen, M., Cheng, AL., et al.[2023]

In a study of 286 patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab, treatment-related hypertension was linked to better progression-free survival, with a median of 12.6 months compared to 6.5 months for those without hypertension.

Conversely, treatment-related fatigue was associated with shorter overall survival, indicating that while hypertension may signal a positive response to treatment, fatigue could indicate poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Tada, T., Kumada, T., Hiraoka, A., et al.[2023]

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]

The combination of atezolizumab and bevacizumab has recently become the new standard of care for patients with advanced hepatocellular carcinoma (HCC), replacing sorafenib, which was the standard for over a decade.

This review highlights practical aspects of using the atezolizumab and bevacizumab combination, including evidence for its efficacy, indications for use, management of side effects, and areas needing further research, making it a valuable resource for clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and bevacizumab as first line therapy in advanced hepatocellular carcinoma: Practical considerations in routine clinical practice. Jain, A., Chitturi, S., Peters, G., et al.[2021]

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]

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]

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 real-world study of 61 patients with hepatocellular carcinoma (HCC), the combination of atezolizumab and bevacizumab showed a median progression-free survival (PFS) of 5.4 months and an objective response rate (ORR) of 35.3%.

The treatment was found to be safe, with a high incidence of adverse events (98.0%), primarily hepatic disorders, but it remained effective even in patients with prior treatment histories or varying liver function as indicated by albumin-bilirubin (ALBI) grades.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice. Iwamoto, H., Shimose, S., Noda, Y., et al.[2021]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40677696/

Systematic review and meta-analysis of real-world evidence Pooled 6- and 12-month OS was 82% (95% CI: 76-86%; I 2 = 80%) and 65% (95% CI: 60-70%; I 2 = 66%). Median OS of patients with CP-A liver ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2589555925001089

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, ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1915745

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

4. tecentriq.com tecentriq.com/hcc/results/how-tecentriq-may-help.html

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 ... Durable partial response (PR) and durable stable disease (SD) are often seen in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12410122/

Real‐World Outcomes of Atezolizumab–Bevacizumab in ... 3.2. Overall Survival ... The median OS was 23.1 months in the cohort with a 12‐month OS of 66% (Figure 1A). Causes of death were deterioration in ...

7. 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 ...