Atezolizumab + Bevacizumab + SBRT for Liver Cancer

Recruiting at 2 trial locations

Overseen By Jennifer Y Wo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must be taking: Anti-HBV therapy

Must not be taking: Anticoagulants, NSAIDs

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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: 7

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and manageability of a treatment combination for individuals with liver cancer that cannot be surgically removed. The treatments include two drugs, atezolizumab (an immunotherapy drug) and bevacizumab (an anti-angiogenic drug), combined with stereotactic body radiation therapy (SBRT), a precise form of radiation. It targets individuals with liver cancer who have non-resectable tumors and up to five liver lesions. Participants should have measurable liver disease and may have received certain treatments previously, excluding major liver surgery. As a Phase 1 trial, the research focuses on understanding how the treatment functions in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there are certain restrictions on medications like full-dose anticoagulants and NSAIDs, and a washout period is required for some prior treatments. It's best to discuss your specific medications with the trial team.

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

A previous study found that combining atezolizumab and bevacizumab with stereotactic body radiation therapy (SBRT) was well-tolerated. Research shows this treatment effectively controlled tumors, achieving local tumor control rates as high as 90%, with only minor side effects. Separate studies of atezolizumab and bevacizumab, already used as a first treatment option for liver cancer, have shown they are generally safe and manageable for patients. This trial is in an early phase, so researchers are closely monitoring for any side effects. However, existing data is promising regarding the safety of these treatments together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab, bevacizumab, and stereotactic body radiation therapy (SBRT) for liver cancer because it brings a unique approach to treatment. Unlike traditional options such as surgery or transarterial chemoembolization (TACE), this combination harnesses the power of immunotherapy through atezolizumab, which helps the immune system target cancer cells more effectively. Bevacizumab adds another layer by inhibiting blood vessel growth that tumors need to thrive. SBRT delivers high doses of radiation precisely to liver tumors, reducing damage to surrounding healthy tissue. Together, these treatments aim to enhance efficacy, potentially leading to better outcomes for patients.

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

Research has shown that combining the drugs atezolizumab and bevacizumab with stereotactic body radiation therapy (SBRT) may offer promise for treating liver cancer. In this trial, participants will receive this combination treatment. Studies have found that radiation therapy with these drugs can help patients with advanced liver cancer live longer without disease progression and may also extend overall survival. Atezolizumab and bevacizumab are already considered safe for treating advanced liver cancer, though they can have some common side effects. Adding SBRT might enhance the effectiveness of these treatments. Early evidence suggests this approach could be particularly beneficial for patients at high risk. ^{1 4 6 7 8}

Who Is on the Research Team?

Jennifer Y Wo, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with unresectable hepatocellular carcinoma (liver cancer), who have not had certain prior treatments, and whose liver function is relatively preserved (Child-Pugh A). They should have no more than 5 liver lesions, no severe portal hypertension or significant heart disease, and must not be pregnant or breastfeeding. Contraception use is required for participants of childbearing potential.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I have had TACE or DEB treatments with a 2-week break before this trial.

My liver is functioning well according to a recent test.

Exclusion Criteria

History of severe anaphylactic reactions to specific substances

My high blood pressure is not well controlled.

I do not have any unmanaged ongoing illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Safety lead-in phase to determine the maximum tolerated dose (MTD) of SBRT with atezolizumab and bevacizumab

18 weeks

6 cycles (1 visit per cycle)

Expanded Study

Participants receive Atezolizumab and Bevacizumab with SBRT, followed by Atezolizumab and Bevacizumab every cycle

Variable, based on safety and benefit

1 visit per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Stereotactic body radiation therapy (SBRT)

Trial Overview The study tests the combination of atezolizumab and bevacizumab drugs with stereotactic body radiation therapy (SBRT) to see if it's safe and tolerable for treating liver cancer that can't be removed by surgery. Participants will receive these medications alongside targeted radiation treatment.

How Is the Trial Designed?

Group I: Stereotactic beam radiation therapy (SBRT) +Atezolizumab + Bevacizumab Experimental Treatment 3 Interventions

Study will begin with a safety lead of 6 participants to determine the maximum tolerated dose (MTD) of Stereotactic beam radiation therapy (SBRT) with atezolizumab and bevacizumab followed by study expansion to 14 more participants after maximum tolerated dose (MTD) is established. Safety Lead-In: 6 cycles/18 weeks (study cycle is 3 weeks/21 days) * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-6: Atezolizumab + Bevacizumab (1x) every 3 weeks Expanded Study: * Cycle 1: Atezolizumab + Bevacizumab (1x) with Stereotactic beam radiation therapy (SBRT) every 1-3 days * Cycles 2-End:Atezolizumab + Bevacizumab (1x) every cycle

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?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

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

Published Research Related to This Trial

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]

Atezolizumab-bevacizumab (atezo-bev) is effective as a first-line treatment for unresectable hepatocellular carcinoma (uHCC), showing a pooled overall survival of 13.8 months and a progression-free survival of 6.86 months across 5400 patients in 47 studies.

Patients with Child-Turcotte-Pugh (CTP) class B cirrhosis experienced similar objective response rates to those with CTP-A cirrhosis, but had shorter progression-free survival, indicating that atezo-bev is safe and effective for both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Kulkarni, AV., Tevethia, H., Kumar, K., et al.[2023]

In a study of 36 patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh B liver function, the combination of atezolizumab and bevacizumab (Ate/Bev) showed modest efficacy, with an objective response rate of 11.1% and a median overall survival of 7.7 months.

However, this treatment was associated with a higher incidence of severe adverse events (44.4% in Child-Pugh B patients) compared to those with Child-Pugh A (15.8%), highlighting the need for careful monitoring and management of side effects in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus bevacizumab in patients with child-Pugh B advanced hepatocellular carcinoma. Cheon, J., Kim, H., Kim, HS., et al.[2023]

In the Phase 3 IMbrave150 trial, atezolizumab combined with bevacizumab showed a similar safety profile to sorafenib in patients with unresectable hepatocellular carcinoma (HCC), regardless of whether they had hepatitis B or C infections.

The rates of viral reactivation were low and comparable between the two treatment groups, with no cases of hepatitis flare reported in patients treated with atezolizumab + bevacizumab, suggesting it is a safe option for patients with HCC and viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab. Hsu, C., Ducreux, M., Zhu, AX., 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]

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 multicenter study involving 30 patients with unresectable hepatocellular carcinoma and extrahepatic portal vein tumor thrombus, the combination of intensity-modulated radiotherapy (IMRT) with systemic atezolizumab and bevacizumab (atezo/bev) resulted in a high objective response rate of 76.6% and a median overall survival of 9.8 months.

The treatment was found to have an acceptable safety profile, with neutropenia being the most common adverse event, and no treatment-related deaths reported, suggesting that this combination therapy could be a promising option for patients with this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy combined with systemic atezolizumab and bevacizumab in treatment of hepatocellular carcinoma with extrahepatic portal vein tumor thrombus: A preliminary multicenter single-arm prospective study. Wang, K., Xiang, YJ., Yu, HM., et al.[2023]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05096715

Atezolizumab+Bevacizumab+SBRT in Unresectable HCC This research study is evaluating the safety and tolerability of the drugs atezolizumab and bevacizumab with stereotactic body radiation therapy (SBRT) for ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10887033/

Outcome of Atezolizumab Plus Bevacizumab Combination ... Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0360301623076265

Radiation Therapy With Combination Therapy of Immune ... We aimed to investigate the effect of RT on the treatment outcomes of ICIs and antiangiogenic combination therapy in patients with advanced-stage HCC.

4. withpower.com withpower.com/trial/phase-1-carcinoma-7-2022-159c9

SBRT + Atezolizumab/Bevacizumab for Liver Cancer The combination of atezolizumab and bevacizumab has been shown to be generally safe for treating advanced liver cancer, with common side effects including ...

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/534721

Atezolizumab and BEvacizumab With STereotactic Body ... To determine the efficacy and safety of atezolizumab-bevacizumab combination therapy plus stereotactic body radiotherapy(SBRT) in patients with advanced ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06595108

Atezolizumab and BEvacizumab With STereotactic Body ... In this study, it is expected to improve the treatment response rate of atezolizumab-bevacizumab therapy, which is currently first-line chemotherapy but has a ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11224977/

Concurrent Atezolizumab Plus Bevacizumab and High- ... Stereotactic body radiation therapy (SBRT) and proton beam radiation (PBT) have demonstrated local tumor control rates up to 90% with minimal ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10565551/

Letter regarding “Feasibility of additional radiotherapy in ... Manzar et al. reported an ORR of 85% within the RT field and median OS of 6.8 months after the start of RT in patients with HCC treated with atezolizumab plus ...