Atezolizumab +/− Bevacizumab for Liver Cancer

(Kirros Trial)

Recruiting in Palo Alto (17 mi)

+61 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Genentech, Inc.

Must not be taking: Immunostimulatory, Immunosuppressive, Live vaccines

Disqualifiers: Pregnancy, Autoimmune disease, CNS metastases, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety and efficacy of atezolizumab and bevacizumab, or atezolizumab alone, as first-line treatment in participants with unresectable, locally advanced or metastatic hepatocellular carcinoma (HCC) with Child-Pugh B7 or B8 cirrhosis.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, it excludes those on systemic immunosuppressive or immunostimulatory medications, so you might need to stop those if applicable.

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

The combination of atezolizumab and bevacizumab has been shown to increase overall survival in patients with advanced liver cancer compared to the previous standard treatment, sorafenib. It is now considered the first choice for treating advanced liver cancer, as it has demonstrated better outcomes in clinical studies. ^{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 safety in treating liver cancer. Common side effects include high blood pressure, fatigue, and protein in the urine. Bleeding was more frequent in patients receiving this treatment compared to another standard treatment, so monitoring for bleeding is recommended. ^{1 3 6 7 8}

How is the drug Atezolizumab plus Bevacizumab unique for liver cancer?

Atezolizumab plus Bevacizumab is unique because it is the first-line treatment specifically approved for advanced liver cancer (hepatocellular carcinoma) and is considered the gold standard for this condition. This combination works by using Atezolizumab to help the immune system attack cancer cells and Bevacizumab to block the blood supply that tumors need to grow. ^{1 3 4 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with advanced liver cancer (HCC) that can't be removed by surgery and who have moderate to severe liver impairment (Child-Pugh B7 or B8). They should not have had previous systemic treatments for their cancer, must be able to perform daily activities with minimal assistance, and women must avoid pregnancy.

Inclusion Criteria

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

I have been active and mostly self-sufficient in the last week.

My blood and organs are functioning well.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atezolizumab with or without Bevacizumab until unacceptable toxicity or loss of clinical benefit

Up to approximately 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Atezolizumab (Checkpoint Inhibitor)
• Bevacizumab (Monoclonal Antibodies)

Trial Overview The study is testing the safety and effectiveness of Atezolizumab alone or combined with Bevacizumab as a first-line treatment. Participants will receive these drugs to see if they help control liver cancer better than current treatments.

Participant Groups

Group I: Cohort B: Atezolizumab Experimental Treatment 1 Intervention

Participants will receive Atezolizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Group II: Cohort A: Atezolizumab+Bevacizumab Experimental Treatment 2 Interventions

Participants will receive Atezolizumab plus Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead 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 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 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 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 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]

In a study of 41 patients with advanced hepatocellular carcinoma who failed first-line treatment with atezolizumab and bevacizumab, the median post-first-line survival was 5.9 months, significantly influenced by liver function status after treatment failure.

Patients with better liver function (Child-Pugh A) had a median survival of 9.6 months compared to only 3.8 months for those with Child-Pugh B and 1.2 months for Child-Pugh C, highlighting the importance of liver reserve and the benefit of receiving second-line therapy, which improved survival to a median of 8.0 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment. Chen, CT., Feng, YH., Yen, CJ., et al.[2022]

References

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

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

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

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

3. 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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Predicting Outcomes of Atezolizumab and Bevacizumab Treatment in Patients with Hepatocellular Carcinoma. [2023]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. [2020]

8. 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]

9. Greece pubmed.ncbi.nlm.nih.gov

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

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

Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment. [2022]