Atezolizumab + Lenvatinib/Sorafenib for Liver Cancer

(IMbrave251 Trial)

Not currently recruiting at 262 trial locations

Overseen By Reference Study ID Number: MO42541 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Disqualifiers: CNS metastases, Hepatic encephalopathy, others

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: Approximately 42 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatment options for individuals with advanced liver cancer, specifically Hepatocellular Carcinoma (HCC), that has worsened despite previous treatments. It evaluates the effectiveness and safety of combining the drug atezolizumab (an immunotherapy) with either lenvatinib or sorafenib, compared to using lenvatinib or sorafenib alone. Participants should have liver cancer that has spread or cannot be surgically removed and have experienced disease progression after previous treatment with atezolizumab plus bevacizumab. This trial might be suitable for those meeting these criteria. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that atezolizumab, when combined with drugs like lenvatinib or sorafenib, has been studied for safety in liver cancer patients. Atezolizumab, already used for some cancers, has shown promising results when paired with other treatments.

Lenvatinib, used after other treatments, has been reported to extend survival in liver cancer patients. Studies indicate that patients lived about 5.4 months without disease progression, suggesting the drug is generally well-tolerated.

Sorafenib has been a standard treatment for liver cancer for some time. When combined with atezolizumab, studies with similar drugs have shown improved survival rates compared to sorafenib alone. However, serious side effects occurred in 38% of patients when atezolizumab was combined with bevacizumab. It is important to remember that every treatment can have side effects, and each person may react differently.

These findings provide a general idea of how atezolizumab, lenvatinib, and sorafenib might be tolerated. Prospective trial participants should consult with a doctor to understand what to expect based on personal health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining atezolizumab with lenvatinib or sorafenib for liver cancer because it introduces a new approach to treatment. Atezolizumab is an immunotherapy drug that helps the body's immune system attack cancer cells, which is different from the standard treatments like lenvatinib or sorafenib alone that target cancer cell growth. This combination aims to enhance the body's natural defenses while also stopping cancer cell proliferation. By utilizing both immune activation and growth inhibition, this approach has the potential to improve outcomes for patients with liver cancer beyond what current treatments offer.

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

This trial will compare the effectiveness of combining atezolizumab with lenvatinib or sorafenib against using lenvatinib or sorafenib alone for treating liver cancer. Research has shown that combining atezolizumab with lenvatinib may be promising. In earlier studies, patients who took lenvatinib after their cancer worsened on atezolizumab with bevacizumab lived for about 5.4 months without the cancer progressing and had a total survival time of 9.8 months. Additionally, the combination of atezolizumab with sorafenib has been studied, and previous research found that atezolizumab with bevacizumab significantly lowers the risk of death compared to using sorafenib alone. These findings suggest that combining atezolizumab with either lenvatinib or sorafenib could be effective for people with advanced liver cancer. ^{1 2 3 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 with advanced liver cancer who've seen their disease progress after treatment with Atezolizumab and Bevacizumab. They should have a good performance status, meaning they're able to carry out daily activities with minimal assistance. Patients must not have certain other cancers or brain metastases that are causing symptoms or require treatment.

Inclusion Criteria

My liver function is classified as Child-Pugh A.

I have a cancer lesion that can be measured and has either not been treated or has grown after treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

My liver cancer is a specific type: fibrolamellar, sarcomatoid, or mixed with bile duct cancer.

I have had cancer spread to the lining of my brain and spinal cord.

I have brain metastases that are untreated or getting worse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab plus lenvatinib or sorafenib, or lenvatinib or sorafenib alone until unacceptable toxicity or loss of clinical benefit

Approximately 42 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
• Lenvatinib
• Sorafenib

Trial Overview The study compares the effectiveness of adding Atezolizumab to Lenvatinib or Sorafenib versus using Lenvatinib or Sorafenib alone in patients whose liver cancer has worsened despite previous treatments. It's a Phase III trial, which means it's testing a treatment already shown to be safe and effective in earlier phases.

How Is the Trial Designed?

Group I: Atezolizumab + Lenvatinib or Sorafenib Experimental Treatment 3 Interventions

Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Group II: Lenvatinib or Sorafenib Active Control 2 Interventions

Participants will receive lenvatinib or sorafenib. Treatment will continue 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?

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

Atezolizumab plus bevacizumab significantly improves progression-free survival (PFS) compared to lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC), based on a meta-analysis of 8 studies involving 3690 patients.

Patients receiving atezolizumab plus bevacizumab experience fewer severe adverse events (grade 3/4) compared to those treated with lenvatinib, indicating a better safety profile, although lenvatinib may be more effective for overall survival in non-viral patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Liu, J., Yang, L., Wei, S., et al.[2023]

In a study of 66 Taiwanese patients with advanced-stage hepatocellular carcinoma (HCC), those treated with lenvatinib showed a higher objective response rate (ORR) of 36.4% compared to 11.4% for sorafenib, indicating better efficacy for lenvatinib.

Both treatments resulted in similar median overall survival (OS) times (9.36 months for lenvatinib vs. 8.36 months for sorafenib), but patients on lenvatinib who achieved an objective tumor response had a significantly improved OS of 11.29 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Lenvatinib and Sorafenib in the Real-World First-Line Treatment of Advanced-Stage Hepatocellular Carcinoma in a Taiwanese Population. Lee, SW., Yang, SS., Lien, HC., et al.[2022]

In a study of 92 patients with unresectable hepatocellular carcinoma (HCC), lenvatinib showed similar efficacy to the combination of atezolizumab and bevacizumab (A+B) in terms of objective response rate, progression-free survival, and overall survival, indicating that both treatments are viable first-line options.

The safety profiles of lenvatinib and A+B were comparable, with similar rates of adverse events and minimal impact on liver function, suggesting that both therapies are safe for patients with HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first-line treatment for unresectable hepatocellular carcinoma. Su, CW., Teng, W., Lin, PT., et al.[2023]

In a study of 304 patients with hepatocellular carcinoma, the combination of atezolizumab and bevacizumab (ATEZO/BEVA) demonstrated significantly better median progression-free survival (8.3 months) and overall survival compared to lenvatinib (LEN) (6.0 months and 20.2 months, respectively).

While ATEZO/BEVA had a lower incidence of severe adverse events like appetite loss and fatigue compared to LEN, it was associated with a higher rate of severe bleeding, indicating a need for careful monitoring in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis. Niizeki, T., Tokunaga, T., Takami, Y., et al.[2022]

In a study of 13 patients, rechallenging with lenvatinib after treatment with atezolizumab plus bevacizumab showed anti-tumor effects, but the duration of the second lenvatinib treatment was significantly shorter (2.8 months) compared to the first treatment (8.7 months).

While lenvatinib re-administration can be effective, it may lead to deterioration in liver function, highlighting the need for careful monitoring of liver health and patient status during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rechallenge With Lenvatinib After Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma. Komatsu, S., Yano, Y., Kido, M., et al.[2022]

In a study of 2205 patients with unresectable HCC, there was no significant overall survival advantage for atezolizumab plus bevacizumab compared to lenvatinib, indicating similar efficacy in first-line treatment.

However, the safety profile favored atezolizumab plus bevacizumab, as it had fewer adverse events, and specific patient groups showed differential benefits, with lenvatinib being more effective for those with non-alcoholic fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Casadei-Gardini, A., Rimini, M., Tada, T., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10670624/

Therapeutic Efficacy and Safety of Lenvatinib after ... Figure 3 shows post-progression survival with atezolizumab plus bevacizumab. The median survival time was 12.5 months (95% CI, 9.3 months—not reached). Figure 3 ...

2. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(25)02457-2/fulltext

Multicenter phase II trial of lenvatinib in patients with ... Lenvatinib shows promising efficacy as a second-line therapy in unresectable HCC. ... Median PFS and OS of 5.4 and 9.8 months, respectively, were ...

3. onclive.com onclive.com/view/lenvatinib-shows-efficacy-in-advanced-hcc-post-progression-on-atezolizumab-bevacizumab

Lenvatinib Shows Efficacy in Advanced HCC Post ... Lenvatinib showed a median PFS of 5.4 months in advanced HCC patients post-atezolizumab/bevacizumab, meeting the primary endpoint. · The study ...

4. ar.iiarjournals.org ar.iiarjournals.org/content/45/3/1117

Efficacy of Lenvatinib and Atezolizumab Bevacizumab ... By regimen, median overall and progression-free survival was 14.9 and 6.1 months for lenvatinib, and “not reached” and 7.9 months for atezolizumab plus ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589555924000661

Atezolizumab/bevacizumab or lenvatinib in hepatocellular ... Atezolizumab/bevacizumab (atezo/bev) and lenvatinib have demonstrated efficacy as first-line therapies for hepatocellular carcinoma (HCC).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11537570/

A comparative analysis in a European real-world cohort Recent studies have reported unexpectedly long survival with lenvatinib (LEN), supporting its use in first-line treatment for HCC. This study ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0168827825024572

Multicenter phase II trial of lenvatinib in patients with ... This study provides the first prospective evidence for the use of lenvatinib as a second-line therapy for patients with unresectable ...