Atezolizumab + Bevacizumab for Liver Cancer

(IMbrave050 Trial)

Not currently recruiting at 272 trial locations

Overseen By Reference Study ID Number: WO41535 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

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

Disqualifiers: Autoimmune disease, Cardiovascular disease, 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)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Up to 33 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two drugs, atezolizumab (an immunotherapy drug) and bevacizumab (an anti-angiogenesis drug), can prevent liver cancer from returning after complete removal or treatment. The study compares this drug combination to monitoring the patient without additional treatment. Suitable participants have had their liver cancer completely removed or treated with specific techniques and face a high risk of recurrence. As a Phase 3 trial, this study serves as the final step before potential FDA approval, allowing participants to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those using certain medications like aspirin, full-dose anticoagulants, and chronic daily non-steroidal anti-inflammatory drugs. 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 well-tolerated in people with liver cancer. In studies involving patients with liver cancer that cannot be surgically removed, this treatment has been tested for both safety and effectiveness.

Reports indicate that this combination helps patients live longer without their cancer worsening. However, like any treatment, side effects can occur. Some patients have experienced high blood pressure, tiredness, and liver-related issues. These side effects are important to monitor, but they can often be managed with medical care.

As the trial is in a later stage, researchers have extensively studied the safety of these drugs. Results so far suggest that many patients can handle the treatment without serious problems. This provides a clearer idea of what to expect, although individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for liver cancer?

Researchers are excited about Atezolizumab combined with Bevacizumab for liver cancer because it offers a fresh approach compared to traditional treatments like surgery and chemotherapy. This combination leverages the immune system, with Atezolizumab boosting the body's immune response to cancer cells, while Bevacizumab inhibits the growth of blood vessels that tumors need to thrive. This dual-action mechanism not only targets the cancer more precisely but also enhances the potential for improved outcomes. Unlike conventional therapies that often come with significant side effects, this combination may offer a more targeted treatment with potentially fewer side effects.

What evidence suggests that atezolizumab plus bevacizumab might be an effective treatment for liver cancer?

Research has shown that using atezolizumab and bevacizumab together effectively treats hepatocellular carcinoma (HCC), a common type of liver cancer. Studies have found that this combination can extend patients' lives and slow disease progression. In this trial, participants in Arm A will receive atezolizumab and bevacizumab until disease recurrence or unacceptable toxicity. One study found that patients with unresectable HCC lived longer and experienced less tumor growth with this treatment compared to others. Another study confirmed that this combination can significantly shrink the cancer for an extended period. These findings suggest it could benefit patients at high risk of HCC recurrence after surgery. ^{2 4 5 6 7}

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 who've had a specific liver cancer (HCC) surgically removed or treated with ablation, and are at high risk of the cancer coming back. They should be fully recovered from treatment, have no major liver vessel invasion or cancer spread outside the liver, and have good liver function (Child-Pugh Class A). Participants need to be in decent health overall (ECOG 0-1), able to use birth control if necessary, and not pregnant.

Inclusion Criteria

I fully recovered from a liver cancer treatment procedure within the last 4 weeks.

My liver function is mildly affected.

I have fully recovered from surgery or ablation within the last 4 weeks.

Exclusion Criteria

I have had a GI fistula, perforation, or an abscess inside my abdomen.

I have a serious blood vessel condition.

My liver cancer is of a specific type (fibrolamellar, sarcomatoid, or mixed).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Atezolizumab plus Bevacizumab until disease recurrence or unacceptable toxicity

Up to 33 months

Active Surveillance

Participants are monitored for recurrence of hepatocellular carcinoma

Up to 91 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 91 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab

Trial Overview The study tests whether adding Atezolizumab plus Bevacizumab after surgery or ablation can prevent HCC from returning compared to just watching patients closely without additional drug treatment. Patients will either receive the drug combo or enter active surveillance where their condition is monitored regularly.

How Is the Trial Designed?

Group I: Arm A (atezolizumab plus bevacizumab) Experimental Treatment 2 Interventions

Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.

Group II: Arm B (active surveillance) Active Control 1 Intervention

Active surveillance of participants.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

Citations

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

Systematic review and meta-analysis of real-world evidence Median OS of patients with CP-A liver function was 20.9 months (95% CI: 15.7-20.9), consistent with IMbrave150 estimates (19.2 months, 95% CI: ...

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. 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. 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 ...