Atezolizumab + Lenvatinib/Sorafenib for Liver Cancer

(IMbrave251 Trial)

Recruiting at 219 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

554 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase III, open-label, multicenter, randomized, two-arm study designed to evaluate the efficacy and safety of atezolizumab plus either lenvatinib or sorafenib versus lenvatinib or sorafenib alone in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have progressed on prior systemic treatment with atezolizumab plus bevacizumab combination.

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.

What data supports the effectiveness of the drug combination Atezolizumab, Lenvatinib, and Sorafenib for liver cancer?

Research shows that Atezolizumab combined with Bevacizumab is more effective than Sorafenib alone for liver cancer, improving survival and disease progression. Lenvatinib also shows better outcomes than Sorafenib, suggesting that these drugs may be effective in treating liver cancer. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Lenvatinib/Sorafenib safe for liver cancer patients?

The safety of Atezolizumab combined with Lenvatinib or Sorafenib for liver cancer specifically isn't directly addressed in the available studies, but Atezolizumab combined with another drug, Bevacizumab, has been used safely in older patients with liver cancer, showing no adverse effects in some cases. ^{1 5 6 7 8}

How is the drug combination of Atezolizumab, Lenvatinib, and Sorafenib unique for liver cancer?

The combination of Atezolizumab, Lenvatinib, and Sorafenib for liver cancer is unique because it explores the use of these drugs together, potentially offering a new approach compared to the standard first-line treatment of Atezolizumab plus Bevacizumab. This combination may provide an alternative for patients who do not respond well to existing treatments. ^{1 2 6 8 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. [2023]

2. Greece pubmed.ncbi.nlm.nih.gov

Rechallenge With Lenvatinib After Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma. [2022]

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

Ranking of transarterial and targeted therapies for advanced hepatocellular carcinoma in the era of immuno-oncology: A network meta-analysis of randomized sorafenib-controlled trials. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Is Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma Superior Even to Lenvatinib? A Matching-Adjusted Indirect Comparison. [2021]

5. France 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. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. [2023]

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

Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first-line treatment for unresectable hepatocellular carcinoma. [2023]

8. Singapore pubmed.ncbi.nlm.nih.gov

Successful multidisciplinary treatment with complete response to atezolizumab plus bevacizumab in a 90-year-old patient with hepatocellular carcinoma recurrence. [2023]

9. Switzerland 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. [2022]