Atezolizumab + Bevacizumab Before Surgery for Liver Cancer

Recruiting at 1 trial location

Overseen By Maen Abdelrahim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Anti-HBV treatment

Must not be taking: High dose steroids, Immunostimulatory agents

Disqualifiers: Active malignancy, Severe cardiac disease, others

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: 7

Duration: 9 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether combining two drugs, atezolizumab (an immunotherapy drug) and bevacizumab (an anti-angiogenic drug), can help the body combat liver cancer before surgery. Both drugs aim to enhance the immune system's ability to attack cancer cells and may prevent the cancer from spreading or returning post-surgery. This trial targets individuals with liver cancer that can be surgically removed and shows no signs of spreading beyond the liver. Participants must have a diagnosis of hepatocellular carcinoma (a common type of liver cancer) and be prepared to undergo a pre-treatment biopsy for research purposes. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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, certain medications like high-dose steroids, some anticoagulants, and immunosuppressive drugs are restricted. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of atezolizumab and bevacizumab is generally safe for people with liver cancer. Studies have found that patients tolerate this treatment well, even those with advanced liver disease. Common side effects include fatigue, high blood pressure, and changes in liver function tests, but these are usually manageable. In previous studies, patients with liver cancer who received this combination therapy experienced positive results, with many showing stable disease or tumor shrinkage without serious side effects. Overall, atezolizumab and bevacizumab appear to be a safe option for treating liver cancer, especially when surgery is possible. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and bevacizumab for liver cancer because it offers a novel approach compared to traditional treatments like surgical resection or transarterial chemoembolization (TACE). Atezolizumab is an immunotherapy that targets the PD-L1 protein, helping the immune system recognize and attack cancer cells more effectively. Bevacizumab, on the other hand, inhibits the growth of blood vessels that tumors need to thrive by targeting the VEGF pathway. This dual approach not only aims to shrink tumors before surgery but also potentially improves surgical outcomes and long-term survival rates by addressing both the immune environment and tumor blood supply, offering hope for enhanced efficacy over existing options.

What evidence suggests that atezolizumab and bevacizumab might be effective treatments for liver cancer?

Research has shown that using atezolizumab and bevacizumab together effectively treats hepatocellular carcinoma, a common type of liver cancer. One study found that patients receiving this combination lived longer and had a lower risk of tumor growth or spread compared to those treated with sorafenib. Another study demonstrated that this combination improved survival rates and delayed cancer progression in patients with difficult-to-remove liver cancer. Real-world evidence supports these findings, showing good response and survival rates in large patient groups. In this trial, participants will receive the combination of atezolizumab and bevacizumab before surgery to explore its potential in preventing cancer recurrence post-surgery. ^{2 3 6 7 8}

Who Is on the Research Team?

Ahmed O. Kaseb

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with resectable liver cancer, who have good liver function (Child-Turcotte-Pugh score A), adequate blood counts, and no severe comorbidities. Participants must not be pregnant or breastfeeding and agree to use two forms of contraception. Exclusions include certain types of liver cancer, recent serious health events like fistulas or bleeding, uncontrolled hypertension, significant pulmonary disease, hypersensitivity to trial drugs, prior treatments for the malignancy within a specific timeframe.

Inclusion Criteria

Serum creatinine ≤ 1.5 × ULN.

I have some limitations in physical activity but can walk and take care of myself.

Women of childbearing potential (WOCBP) and men with partners of child bearing potential agree to prevent pregnancy using two forms of contraception from the date of Informed Consent through 5 months post last dose of study drug.

Exclusion Criteria

You have experienced severe allergic reactions to certain types of medications called chimeric or humanized antibodies.

I have a serious heart condition, such as heart failure or unstable angina.

I have been treated for cancer, have another active cancer, or had cancer in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab and bevacizumab intravenously every 21 days for up to 3 cycles

9 weeks

3 visits (in-person)

Surgery

Participants undergo surgery to remove resectable liver cancer

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Therapeutic Conventional Surgery

Trial Overview The study tests atezolizumab plus bevacizumab before surgery in patients with resectable hepatocellular carcinoma. It aims to see if this combination can help the immune system attack the cancer more effectively and prevent it from returning post-surgery by inhibiting tumor growth and spread.

How Is the Trial Designed?

Group I: Treatment (atezolizumab, bevacizumab) Experimental Treatment 3 Interventions

Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery during week 12.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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 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 216 patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (AtezoBev), the treatment demonstrated a median overall survival of 14.9 months and a median progression-free survival of 6.8 months, indicating its efficacy in a real-world clinical setting.

Patients with impaired liver function (Child-Pugh class B) experienced similar rates of treatment-related adverse events compared to those with better liver function (Child-Pugh class A), suggesting that AtezoBev is tolerable and may be a viable option for this underserved population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. D'Alessio, A., Fulgenzi, CAM., Nishida, N., 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]

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 therapy of atezolizumab and bevacizumab shows potential as a treatment option for patients with both hepatocellular carcinoma and gastric adenocarcinoma.

This finding suggests a possible new approach for managing these concurrent cancers, although further studies are needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatocellular carcinoma with gastric adenocarcinoma treated with atezolizumab and bevacizumab. Suga, T., Kimura, Y., Furuya, K., 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]

Bevacizumab (Avastin) effectively targets VEGF to inhibit tumor angiogenesis, showing a safety profile that includes mostly mild to moderate side effects such as hypertension and proteinuria, which are manageable in clinical settings.

The side effects associated with bevacizumab, including rare but serious events like gastrointestinal perforation and arterial thrombosis, do not typically exacerbate the toxicity of standard chemotherapy, making it a suitable adjunct treatment for metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. Gordon, MS., Cunningham, D.[2015]

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

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 ...

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. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38756146/

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. 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 ...

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 ...