Immunotherapy for Liver Cancer

Recruiting at 41 trial locations

Overseen By Reference Study ID Number: GO44457 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Anticoagulants, Thrombolytics, NSAIDs

Disqualifiers: Extrahepatic disease, Hypertension, Co-infection, 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)

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 12 weeks

62 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is designed with the flexibility to open new treatment arms as new agents become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you cannot be on chronic daily treatment with NSAIDs (non-steroidal anti-inflammatory drugs) and should not have used full-dose anticoagulants or thrombolytic agents within 10 days before starting the study treatment.

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

Research shows that the combination of Atezolizumab and Bevacizumab is now the standard treatment for advanced liver cancer, as it has been proven to be more effective than the previous standard drug, Sorafenib. This combination works by enhancing the body's immune response against cancer and has shown improved outcomes in patients with liver cancer. ^{1 2 3 4 5}

Is the immunotherapy treatment for liver cancer safe?

The combination of atezolizumab and bevacizumab has been generally safe for treating advanced liver cancer, but some patients experienced side effects like high blood pressure, fatigue, and protein in urine. Serious side effects, such as bleeding and rare cases of brain inflammation (encephalitis), have also been reported. ^{2 6 7 8 9}

How does the drug atezolizumab plus bevacizumab differ from other treatments for liver cancer?

Atezolizumab plus bevacizumab is unique because it combines two drugs that work together to boost the immune system's ability to fight liver cancer. Atezolizumab blocks a protein that helps cancer cells hide from the immune system, while bevacizumab stops the growth of blood vessels that feed tumors, making this combination a new standard for treating advanced liver cancer. ^{1 2 4 8 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with Hepatocellular Carcinoma (HCC) that can be surgically removed. They must have a confirmed diagnosis, measurable disease, good performance status, and proper liver function. No prior treatments for HCC are allowed, and they should not have any serious co-infections or conditions that could complicate surgery or treatment.

Inclusion Criteria

My liver cancer diagnosis was confirmed following specific guidelines.

Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator

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

Exclusion Criteria

I have had a severe hypertension crisis or brain issues due to high blood pressure.

I have untreated or partially treated varices in my esophagus or stomach that may bleed.

I had bleeding from esophageal or stomach varices in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to three cycles of neoadjuvant immunotherapy combinations until surgery or unacceptable toxicity

Up to 12 weeks

Surgery

Participants undergo surgery to resect hepatocellular carcinoma

Follow-up

Participants are monitored for safety and effectiveness after surgery, including relapse-free survival and overall survival

Up to 3 years

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab
• Tiragolumab
• Tobemstomig

Trial Overview The study tests combinations of immunotherapy drugs (Tobemstomig, Tiragolumab, Atezolizumab, Bevacizumab) given before surgery to remove the cancer. It's flexible to adapt by adding new treatments or stopping ones based on results and safety.

Participant Groups

Group I: Tobe + Bev Experimental Treatment 2 Interventions

Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. Enrollment is closed.

Group II: Atezo + Bev +Tira Experimental Treatment 3 Interventions

Participants in the atezolizumab plus bevacizumab plus tiragolumab (Atezo + Bev +Tira) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

Group III: Atezo + Bev Experimental Treatment 2 Interventions

Participants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

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

The CRAFITY score, developed from baseline serum alpha-fetoprotein and C-reactive protein levels, effectively predicts overall survival in patients with hepatocellular carcinoma (HCC) undergoing immunotherapy, with a significant correlation between score levels and median survival times.

Patients with a CRAFITY-low score (0 points) had the longest median overall survival of 27.6 months, while those with a CRAFITY-high score (2 points) had a median survival of only 6.4 months, indicating that this score can help guide treatment decisions and patient counseling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score. Scheiner, B., Pomej, K., Kirstein, MM., et al.[2022]

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]

In a study of 1447 patients treated with tyrosine-kinase inhibitors for hepatocellular carcinoma, only 29% were eligible for the combination therapy of atezolizumab-bevacizumab based on the IMbrave-150 trial criteria, indicating limited real-world applicability.

Eligible patients showed a median overall survival of 14.9 months, which was longer than non-eligible patients, suggesting that those who meet the criteria have better baseline health and cancer characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors. Stefanini, B., Bucci, L., Santi, V., et al.[2022]

Atezolizumab combined with bevacizumab is now the recommended first-line treatment for patients with unresectable or advanced hepatocellular carcinoma (HCC), supported by various national and international guidelines.

Combination therapies, including local treatments with targeted drugs like sorafenib and lenvatinib, have shown significant improvements in patient outcomes, indicating a promising direction for advanced HCC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Advances in targeted and immune therapies for hepatocellular carcinoma]. Nan, YM., Miao, TG.[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]

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]

A 70-year-old woman with advanced hepatocellular carcinoma developed severe encephalitis after just one cycle of the combination therapy with atezolizumab and bevacizumab, highlighting a rare but serious adverse effect of this treatment.

Rapid immunosuppressive treatment with high-dose steroids and plasmapheresis led to clinical improvement in the patient's encephalitis, although she ultimately succumbed to progressive liver cancer, indicating the need for careful monitoring of neurological symptoms in patients receiving immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab and bevacizumab-induced encephalitis in advanced hepatocellular carcinoma: Case report and literature review. Özdirik, B., Jost-Brinkmann, F., Savic, LJ., et al.[2023]

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 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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

Potential feasibility of atezolizumab-bevacizumab therapy in patients with hepatocellular carcinoma treated with tyrosine-kinase inhibitors. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Advances in targeted and immune therapies for hepatocellular carcinoma]. [2022]

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

FDA Approval Summary: Atezolizumab Plus Bevacizumab for the Treatment of Patients with Advanced Unresectable or Metastatic Hepatocellular Carcinoma. [2022]

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

Atezolizumab and bevacizumab-induced encephalitis in advanced hepatocellular carcinoma: Case report and literature review. [2023]

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

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

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

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. [2022]

10. 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]