Atezolizumab +/− Bevacizumab for Liver Cancer

(Kirros Trial)

Recruiting at 66 trial locations

Overseen By Reference Study ID Number: ML44719 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genentech, Inc.

Must not be taking: Immunostimulatory, Immunosuppressive, Live vaccines

Disqualifiers: Pregnancy, Autoimmune disease, CNS metastases, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 36 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety of a new treatment for individuals with liver cancer that cannot be surgically removed. Researchers are testing the drug atezolizumab (Tecentriq), alone or with bevacizumab (Avastin), for advanced or metastatic liver cancer. It targets individuals who have not received prior systemic treatment and whose condition cannot be managed with surgery or local treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that the combination of atezolizumab and bevacizumab is generally well-tolerated by patients with advanced liver cancer. Studies have found that this combination can effectively treat cancer and improve survival rates. Although some side effects may occur, many patients have used this treatment successfully, indicating it is relatively safe.

Atezolizumab alone has a similar safety profile. It treats liver cancer and other conditions, and while some patients might experience side effects, it is considered safe enough for widespread use in treatment plans.

Earlier trials have tested both treatments, providing evidence that they are safe for most people. However, individual reactions can vary, so discussing potential risks with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Atezolizumab and Bevacizumab for liver cancer because they work differently from standard treatments. While most existing liver cancer therapies focus on targeting tumor growth directly, Atezolizumab is an immune checkpoint inhibitor. This means it helps the immune system recognize and destroy cancer cells more effectively. Bevacizumab, on the other hand, is an angiogenesis inhibitor, which means it stops tumors from creating new blood vessels, essentially starving them of nutrients. This dual approach could potentially lead to more effective outcomes by both boosting the immune response and cutting off the tumor's lifeline.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research shows that combining atezolizumab and bevacizumab effectively treats advanced liver cancer. In this trial, participants in Cohort A will receive this combination. Studies indicate that it helps patients live longer and slows tumor growth more effectively than sorafenib. One study found that this combination reduced the risk of death by 42%. Participants in Cohort B will receive atezolizumab alone, which has also shown potential in treating liver cancer. Both treatments aim to extend the lives of patients with liver cancer that cannot be surgically removed and improve their quality of life. ^{4 5 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab

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.

How Is the Trial Designed?

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.

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?

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

Published Research Related to This Trial

In a phase 1b study involving 223 patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab resulted in a significantly longer median progression-free survival of 5.6 months compared to 3.4 months for atezolizumab alone, indicating enhanced efficacy of the combination treatment.

The most common serious treatment-related adverse events included hypertension and proteinuria, with a treatment-related death rate of 3% in the combination group, suggesting that while the combination therapy is effective, it does carry some safety risks that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lee, MS., Ryoo, BY., Hsu, CH., et al.[2020]

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]

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]

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 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]

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]

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]

The combination of atezolizumab and bevacizumab (AB) has been established as the preferred treatment for hepatocellular carcinoma (HCC) patients at Barcelona Liver Cancer Clinic stage C, showing better outcomes than sorafenib.

Despite its effectiveness, many patients do not experience significant survival benefits or responses, highlighting the urgent need for predictive biomarkers to guide treatment decisions for those receiving AB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40905621/

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 comparable ...

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00645

Clinical Outcomes and Histologic Findings of Patients With ... The median progression-free survival was 23.2 months for patients with durable PR and 13.2 months for those with durable SD. In the real-world ...

5. 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 ...

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. tecentriq-hcp.com tecentriq-hcp.com/hcc.html

First Line Treatment for Unresectable or Metastatic HCC Important Safety Information · Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. There are no available ...

8. 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 ...