Atezolizumab + Bevacizumab +/− SRF388 for Liver Cancer

No longer recruiting at 56 trial 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for advanced liver cancer. Researchers aim to determine if adding SRF388 (also known as CHS-388 or Casdozokitug) to the existing drugs atezolizumab and bevacizumab is more effective than using just the two drugs with a placebo (inactive substance). Participants will receive either the treatment with SRF388 or the standard treatment with a placebo. Individuals with advanced liver cancer that cannot be surgically removed and who have not received prior systemic treatment might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that combining SRF388 with atezolizumab and bevacizumab is generally safe. Previous studies found that patients tolerate this treatment mix well. Reports from these studies indicate that any side effects are usually manageable and do not outweigh the potential benefits.

Atezolizumab and bevacizumab are already used together for other conditions, suggesting they are relatively safe. Adding SRF388 also appears safe based on current findings. Overall, this treatment has a promising safety record, making it a potential option for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver cancer because they combine Atezolizumab and Bevacizumab with or without SRF388, potentially offering a new approach to tackling the disease. Atezolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells, while Bevacizumab targets the blood vessels that feed tumors, starving them. SRF388, a newer compound, aims to enhance this effect by inhibiting IL-27, a cytokine that can suppress immune response against tumors. This combination could lead to a more effective treatment regimen than the current standard, which typically involves targeted therapies and chemotherapy.

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

Research has shown that combining SRF388 with atezolizumab and bevacizumab, which participants in Arm A of this trial may receive, may help treat advanced liver cancer. Studies have found that this combination can lead to lasting improvements, demonstrating effectiveness over time. In 17.2% of cases, the cancer completely disappears, indicating that the treatment can significantly shrink or eliminate tumors in some patients. This combination blocks proteins that help cancer grow, which may explain its effectiveness. Overall, evidence suggests this treatment could improve outcomes for liver cancer patients. ^{2 3 4 6 7}

Who Is on the Research Team?

Koho Iizuka, MD

Principal Investigator

Coherus Oncology, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Coherus Oncology, Inc.

Lead Sponsor

Surface Oncology

Lead Sponsor

Trials

6

Recruited

730+

Published Research Related to This Trial

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 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]

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 (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 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]

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 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]

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 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 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]

Citations

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Study Details | NCT05359861 | Trial of Atezolizumab and ...

This is a Phase 2 trial designed to evaluate the efficacy and safety of SRF388 in combination with atezolizumab plus bevacizumab (Arm A) compared to placebo in ...

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This open-label Ph 2 trial examined the potential antitumor activity and safety of casdozo with PD-L1 and VEGF blockade in uHCC.

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Casdozokitug, in combination with atezolizumab/bevacizumab, final data demonstrate durability of response and improvement in depth of response including a 17.2 ...

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Casdozokitug Plus Atezolizumab/Bevacizumab Yields ...

We previously performed a phase 1 study of casdozokitug as a single agent, and it demonstrated favorable safety as well as antitumor activity.

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Casdozokitug, combined with atezolizumab and bevacizumab, shows durable responses and a 17.2% complete response rate in HCC treatment.

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Study Details | NCT05359861 | Trial of Atezolizumab and ...

This is a Phase 2 trial designed to evaluate the efficacy and safety of SRF388 in combination with atezolizumab plus bevacizumab (Arm A) compared to placebo in ...

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ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.470

Results from a phase 2 study of triplet blockade of the IL-27 ...

Triplet blockade of the IL-27, VEGF, and PD-(L)1 pathways with casdozo/atezo/bev has an acceptable safety profile to date with promising antitumor activity in ...