Atezolizumab + Bevacizumab for Liver Cancer

(AB7 Trial)

Recruiting at 6 trial locations

Overseen By Gabrielle Tiggs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kristen Spencer

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Fibrolamellar HCC, Autoimmune 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: 3

Duration: Up to 1 year

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive medications, you must stop them 6 weeks before starting the trial, unless they are low-dose corticosteroids or certain other exceptions.

What data supports the effectiveness of the drug combination Atezolizumab and Bevacizumab for liver cancer?

Research shows that the combination of atezolizumab and bevacizumab improves overall survival in patients with advanced liver cancer compared to the previous standard treatment, sorafenib. This combination is now considered the gold standard for first-line treatment of advanced liver cancer. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Bevacizumab safe for treating liver cancer?

The combination of Atezolizumab and Bevacizumab has been studied for liver cancer and is generally considered safe, but it can cause side effects like high blood pressure, tiredness, and protein in the urine. Bleeding was more common in patients taking this combination compared to another treatment, so monitoring is recommended. ^{2 6 7 8 9}

How is the drug combination of atezolizumab and bevacizumab unique for liver cancer treatment?

The combination of atezolizumab and bevacizumab is unique because it is the new standard first-line treatment for advanced liver cancer, offering improved survival compared to previous options like sorafenib. This combination therapy represents a significant advancement in managing liver cancer across various stages. ^{1 2 5 10 11}

What is the purpose of this trial?

This will be a nonrandomized, single arm feasibility study with the primary goal of evaluating the safety profile of the combination of atezolizumab and bevacizumab in patients with advanced/metastatic HCC with Child-Pugh B7 and B8 liver disease who have received no prior systemic therapy.

Research Team

Howard S. Hochster

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for adults with advanced liver cancer (Hepatocellular Carcinoma) who haven't had systemic therapy before. They should have a specific level of liver dysfunction (Child-Pugh B7 or B8), be able to perform daily activities with little help, and agree to use contraception. People can't join if they're on high-dose steroids, have certain heart or lung conditions, uncontrolled other diseases, or are expected to need treatment for another cancer within two years.

Inclusion Criteria

I have at least one cancer spot that hasn't been treated yet.

Written informed consent and HIPAA authorization for release of personal health information

As determined by the enrolling physician or protocol designee, ability of the subject to understand a written informed consent document, and ability and willingness to comply with study procedures

Exclusion Criteria

I have significant fluid buildup in my abdomen.

I do not have another cancer that needs treatment within 2 years.

I have had radiation for any painful cancer spots before joining.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab 1,200 mg IV and bevacizumab 15 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity

Up to 1 year

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab

Trial Overview The study tests the safety of combining Atezolizumab and Bevacizumab in patients with advanced liver cancer. It's a single group trial where all participants receive both drugs without being compared to another treatment or placebo.

Participant Groups

Group I: Study Treatment Experimental Treatment 2 Interventions

Atezolizumab 1,200 mg IV and bevacizumab 15 mg/kg IV every 3 weeks (on day 1 of each 21-day cycle). Treatment will continue until disease progression or development of unacceptable toxicity.

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?

Kristen Spencer

Lead Sponsor

Trials

2

Recruited

130+

Howard S. Hochester

Lead Sponsor

Trials

1

Recruited

50+

Howard S Hochster

Lead Sponsor

Trials

1

Recruited

50+

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

Rutgers Cancer Institute of New Jersey

Collaborator

Trials

72

Recruited

22,200+

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]

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]

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]

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]

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 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 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 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 plus bevacizumab (Atez/Bev) is safe and effective for treating elderly patients with unresectable hepatocellular carcinoma (HCC), as shown in a study of 317 patients where age did not negatively impact survival outcomes.

There were no significant differences in treatment-related adverse events between elderly and non-elderly patients, indicating that Atez/Bev can be administered safely across different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: A multicenter analysis. Tada, T., Kumada, T., Hiraoka, A., et al.[2022]

References

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

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

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

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

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

Atezolizumab and bevacizumab as first line therapy in advanced hepatocellular carcinoma: Practical considerations in routine clinical practice. [2021]

4. England 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. [2023]

5. 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]

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

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

8. United States 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. [2023]

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

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice. [2021]

10. Greece pubmed.ncbi.nlm.nih.gov

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

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

Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: A multicenter analysis. [2022]