Atezolizumab + Bevacizumab + Y^90 Radioembolization for Liver Cancer

Overseen By Brandy Haydel

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Antibiotics, Immunosuppressants, Immunostimulants, others

Disqualifiers: Autoimmune diseases, Cardiovascular disease, 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

Duration: 9 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for liver cancer, specifically hepatocellular carcinoma (HCC). The treatments include atezolizumab (an immunotherapy drug), bevacizumab (a targeted therapy drug), and Y^90 radioembolization (a type of radiation therapy). The goal is to determine if this combination can prepare patients for liver transplants by shrinking tumors or preventing their growth. Suitable candidates have liver cancer within certain size limits or are considered high-risk, without cancer spread outside the liver or into blood vessels. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments can benefit more patients.

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

The trial does not clearly state if you need to stop your current medications. However, it mentions that certain medications, like systemic immunosuppressive drugs, should not be taken within two weeks before starting the study treatment. It's best to discuss your specific medications with the trial team.

What is the safety track record for atezolizumab, bevacizumab, and Y^90 radioembolization?

Research has shown that combining atezolizumab, bevacizumab, and Y^90 radioembolization is generally safe for liver cancer patients. Atezolizumab and bevacizumab, already approved for other uses, have a known safety profile. Y^90 radioembolization, which uses tiny radiation beads to target liver cancer, has demonstrated safety results similar to treatments like Lenvatinib and Nivolumab.

One study found no unexpected safety issues with this combination. However, two patients in the study died during follow-up. Despite this, overall survival rates at 6 and 12 months were 88.9% and 76.2%, respectively. This suggests that while risks exist, the treatment can be safe for most patients.

As with any treatment, side effects may occur. Earlier studies suggest this combination does not introduce new or unexpected safety concerns. Always discuss with a doctor what this might mean for individual circumstances. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of Atezolizumab, Bevacizumab, and Y^90 Radioembolization for liver cancer because it represents a novel approach compared to existing treatments like sorafenib or lenvatinib, which are primarily oral medications targeting cancer growth. This combination harnesses the power of immunotherapy with Atezolizumab, which helps the immune system recognize and attack cancer cells, and Bevacizumab, which inhibits the growth of blood vessels that feed tumors. Additionally, Y^90 Radioembolization delivers targeted radiation directly to the liver tumor, potentially enhancing the effectiveness of the immune and anti-angiogenesis therapies. Together, these therapies may offer a more comprehensive attack on liver cancer, potentially improving outcomes for patients who meet specific criteria.

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

This trial will evaluate the combination of atezolizumab and bevacizumab with Y^90 radioembolization for treating liver cancer. Research has shown that this combination holds promise for treating hepatocellular carcinoma (HCC). Studies have found it can be as effective as other standard treatments for liver cancer. Specifically, 76.2% of patients who received this combination were still alive after 12 months. Atezolizumab and bevacizumab enhance the immune system's ability to fight cancer cells, while Y^90 radioembolization directly targets and destroys tumors in the liver. These findings suggest this combination could be effective for people with liver cancer, especially those considering a transplant. Participants in this trial will be divided into two cohorts based on specific criteria to assess the treatment's effectiveness. ^{1 3 4 6 7}

Who Is on the Research Team?

Parissa Tabrizian, MD

Principal Investigator

Mount Sinai Liver Cancer Program

Josep Llovet, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for individuals with hepatocellular carcinoma (HCC), a type of liver cancer. It's aimed at those within Milan Criteria but with high AFP levels, as a bridge to transplant, and those beyond Milan Criteria, potentially downstaging them to qualify for a liver transplant.

Inclusion Criteria

Signed Informed Consent Form

Ability to comply with the study protocol

Availability of a representative tumor specimen suitable for determination of PD-L1 status via central testing

Exclusion Criteria

AFP ≥ 1000 ng/ml

Active or history of autoimmune disease or immune deficiency

Prior allogeneic stem cell, solid organ, or multi-organ transplantation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Y^90 radioembolization in combination with atezolizumab and bevacizumab

9 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Periodic visits for assessment

Post-transplant monitoring

Participants are monitored for recurrence and transplant-related outcomes

1 year post-transplant

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Y^90 Radioembolization

Trial Overview The study tests combining Y^90 Radioembolization (a targeted radiation therapy) with systemic Atezolizumab and Bevacizumab in patients with HCC. The goal is to see if this combination can help make patients eligible for liver transplantation.

How Is the Trial Designed?

Group I: Cohort B: participants within Milan Criteria with AFP ≥ 400 ng/ml at enrollment. Experimental Treatment 3 Interventions

Atezolizumab and Bevacizumab in Combination with Y\^90 Radioembolization

Group II: Cohort A: participants beyond Milan Criteria upon enrollment Experimental Treatment 3 Interventions

Atezolizumab and Bevacizumab in Combination with Y\^90 Radioembolization

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37988840/

Efficacy of transarterial radioembolization using Y-90 resin ... In HCC patients receiving treatment, TARE using Y-90 resin microspheres may achieve comparable effectiveness outcomes compared with AB.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804923007293

Efficacy of transarterial radioembolization using Y-90 resin ... In HCC patients receiving treatment, TARE using Y-90 resin microspheres may achieve comparable effectiveness outcomes compared with AB.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07059494

Atezolizumab and Bevacizumab in Combination With Y^90 ... Assessment of efficacy of Y^90 in combination with atezolizumab and bevacizumab, pre- and post- transplant as defined Recurrence-free survival (RFS) rate at 1 ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16231

Introducing yttrium-90 radioembolization to atezolizumab ... Two patients died during follow-up, with 6-month and 12-month OS rates of 88.9% (95%CI: 43.3-98.4%) and 76.2% (95%CI: 33.2-93.5%), respectively.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10742675/

Safety and Efficacy of Concurrent Atezolizumab/ ... Abstract. To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07059494

Atezolizumab and Bevacizumab in Combination With Y^90 ... A single institution, single arm, two-cohort feasibility trial to evaluate the combination of locoregional Y^90 therapy with systemic atezolizumab and ...

7. bmcgastroenterol.biomedcentral.com bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-022-02528-y

Overall survival and toxicity of Y90 radioembolization for ... The current study found that BCLC-C patients treated with resin Y90 had OS comparable to those identified with Lenvatinib and Nivolumab.