Atezolizumab + Bevacizumab +/− SRF388 for Liver Cancer

Recruiting in Ann Arbor (>99 mi)

+34 other locations

Overseen By Hillary O'Kelly, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Coherus Biosciences, Inc.

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Autoimmune, HIV, Hepatitis, 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

Compensation: Varies

Number of Visits: Unknown

134 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on chronic steroid therapy or systemic immunosuppressive medications, you may not be eligible to participate.

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

The combination of Atezolizumab and Bevacizumab has been shown to improve overall survival and progression-free survival in patients with advanced liver cancer compared to the standard treatment with sorafenib. This combination is now considered a new standard of care for this condition. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Bevacizumab safe for liver cancer patients?

The combination of Atezolizumab and Bevacizumab has been shown to be generally safe for liver cancer patients, with common side effects including high blood pressure, fatigue, and protein in the urine. However, there is a higher risk of bleeding, and serious side effects occurred in some patients, including a few deaths. ^{2 4 6 7 8}

What makes the drug combination of Atezolizumab, Bevacizumab, and SRF388 unique for liver cancer?

This drug combination is unique because it includes Atezolizumab and Bevacizumab, which are already approved as a first-line treatment for advanced liver cancer, and adds SRF388, potentially enhancing the treatment's effectiveness. Atezolizumab helps the immune system attack cancer cells, while Bevacizumab inhibits blood vessel growth that tumors need to grow, and SRF388 may offer additional benefits, although its specific role in this combination is still being studied. ^{3 4 5 9 10}

What is the purpose of this trial?

This trial tests SRF388 with atezolizumab and bevacizumab in patients with advanced liver cancer. The treatment aims to enhance immune response and block blood supply to tumors. Atezolizumab and bevacizumab have become the standard of care for advanced hepatocellular carcinoma, replacing sorafenib which was the standard for over ten years.

Research Team

Koho Iizuka, MD

Principal Investigator

Coherus Biosciences, Inc.

Eligibility Criteria

Adults with advanced liver cancer (Hepatocellular Carcinoma) who haven't had systemic treatment for their condition can join this trial. They should be in relatively good health, able to perform daily activities with ease or slight difficulty, and have a liver that's still working well. Pregnant women can't participate, and those who can have children must use birth control.

Inclusion Criteria

My liver disease is mild.

I haven't had any treatments for my advanced liver cancer.

Laboratory values indicative of adequate organ function as defined in the protocol

Exclusion Criteria

I frequently need procedures to remove excess fluid from my body.

I am on or might need strong medication to suppress my immune system.

I have an autoimmune disease or immune deficiency, but it's controlled or minor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-In

A minimum of 6 patients and up to 30 patients will be enrolled in an open-label Lead-In to assess the preliminary safety and tolerability of SRF388 with atezolizumab plus bevacizumab

Not specified

Open-label treatment

Randomized Phase

Approximately 104 patients will be randomized to receive either SRF388 with atezolizumab plus bevacizumab or placebo with atezolizumab plus bevacizumab

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab
• Placebo
• SRF388

Trial Overview The study is testing the effectiveness of SRF388 combined with Atezolizumab and Bevacizumab versus a placebo mixed with the same two drugs in treating first-line advanced liver cancer. Participants are randomly assigned to one of these groups to compare results.

Participant Groups

Group I: Lead-In Experimental Treatment 3 Interventions

A minimum of 6 patients and up to 30 patients will be enrolled in an open-label Lead-In to assess the preliminary safety and tolerability of SRF388 with atezolizumab plus bevacizumab.

Group II: Arm B: Placebo in combination with atezolizumab plus bevacizumab Experimental Treatment 3 Interventions

Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab.

Group III: Arm A: SRF388 in Combination with atezolizumab plus bevacizumab Experimental Treatment 3 Interventions

Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab.

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?

Coherus Biosciences, Inc.

Lead Sponsor

Trials

19

Recruited

3,700+

Surface Oncology

Lead Sponsor

Trials

6

Recruited

730+

Findings from Research

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]

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]

In a study of 766 patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab, those who met the IMbrave150 trial inclusion criteria had significantly longer overall survival (16.3 months) compared to those who did not (14.3 months).

Among patients who did not meet the IMbrave150 criteria, those with a better liver function (ALBI grade 1) experienced a notable survival benefit, with a median overall survival of 16.7 months compared to 5.9 months for those with ALBI grade 2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis? Rimini, M., Persano, M., Tada, T., et al.[2023]

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 shows efficacy in patients with advanced hepatocellular carcinoma (aHCC) who have previously received systemic therapy, achieving an objective response rate of 32% and a median overall survival of 16 months based on a study of 50 patients.

The safety profile of this treatment was consistent with earlier studies, with 14% of patients experiencing severe adverse events, including three deaths, indicating that while effective, careful monitoring for serious side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience. Sinner, F., Pinter, M., Scheiner, B., 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]

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]

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 phase III study involving 501 patients with unresectable hepatocellular carcinoma (HCC), those with baseline BCLC stage B disease showed a trend towards improved overall survival (OS) and progression-free survival (PFS) when treated with atezolizumab plus bevacizumab compared to sorafenib, with hazard ratios of 0.63 and 0.64, respectively.

The objective response rates (ORR) were significantly higher for the atezolizumab plus bevacizumab group (43% and 50% using different assessment criteria) compared to the sorafenib group (26% and 30%), indicating that this combination therapy may provide more effective tumor response in patients with BCLC stage B HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMbrave150: Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma: An Exploratory Analysis of the Phase III Study. Kudo, M., Finn, RS., Galle, PR., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Atezolizumab plus Bevacizumab: A Novel Breakthrough in Hepatocellular Carcinoma. [2022]

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

Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis? [2023]

5. England 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience. [2023]

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

Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: A multicenter analysis. [2022]

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

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

9. Greece pubmed.ncbi.nlm.nih.gov

Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

IMbrave150: Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Barcelona Clinic Liver Cancer Stage B Unresectable Hepatocellular Carcinoma: An Exploratory Analysis of the Phase III Study. [2023]