RP3 + Atezolizumab + Bevacizumab for Liver Cancer

Recruiting in Palo Alto (17 mi)

+30 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Replimune Inc.

Must be taking: Anti-PD-1, Anti-PD-L1

Must not be taking: Antivirals, Anticoagulants

Disqualifiers: HIV, Active tuberculosis, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate whether treatment with RP2 can provide efficacy as 2L treatment combined with atezolizumab plus bevacizumab in patients with locally advanced unresectable, recurrent, and/or metastatic HCC.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like systemic anticancer therapies, live vaccines, or botanical preparations within specific time frames before the trial starts. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of atezolizumab and bevacizumab improves overall survival in patients with advanced liver cancer compared to the previous standard treatment, sorafenib. This combination is now considered the standard first-line treatment for advanced liver cancer. ^{1 2 3 4 5}

Is the combination of RP3, Atezolizumab, and Bevacizumab safe for humans?

Atezolizumab and Bevacizumab have been studied together for liver cancer, showing some common side effects like high blood pressure, tiredness, and protein in urine. Bleeding was more frequent in patients using this combination compared to another treatment. It's important to monitor for these effects, especially if you have liver cancer. ^{6 7 8 9 10}

What makes the RP3 + Atezolizumab + Bevacizumab treatment for liver cancer unique?

The RP3 + Atezolizumab + Bevacizumab treatment is unique because it combines a new investigational drug, RP3, with the established combination of atezolizumab and bevacizumab, which is already a standard first-line treatment for advanced liver cancer. This combination aims to enhance the effectiveness of the existing therapy by potentially introducing a novel mechanism of action with RP3. ^{1 5 11 12 13}

Research Team

May Cho, MD

Principal Investigator

Replimune Inc.

Eligibility Criteria

Adults with advanced, inoperable or metastatic liver cancer (Hepatocellular Carcinoma) who have either not had systemic therapy or have tried one that includes anti-PD-1/PD-L1. They must be generally healthy, with proper kidney, blood and liver function, and no recent use of investigational drugs. Women of childbearing age need a negative pregnancy test and agree to contraception.

Inclusion Criteria

I agree to provide a recent or new tumor biopsy for the study.

I am able to understand and sign the consent form.

I have a tumor that is at least 1cm big, or a lymph node that is at least 1.5cm in its shortest dimension.

Exclusion Criteria

My liver cancer has been confirmed by tissue analysis.

I have a history of serious heart problems.

I am HIV positive.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RP2 in combination with atezolizumab and bevacizumab as second-line therapy

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

135 days after last dose

Treatment Details

Interventions

• Atezolizumab (Monoclonal Antibodies)
• Bevacizumab (Monoclonal Antibodies)
• RP3 (Virus Therapy)

Trial Overview The trial is testing RP3 combined with atezolizumab plus bevacizumab as first- or second-line treatments for Hepatocellular Carcinoma. It's an open-label Phase 2 study where all participants know which treatment they're getting.

Participant Groups

Group I: RP2+Bevacizumab and Atezolizumab Experimental Treatment 3 Interventions

Patients with locally advanced unresectable, recurrent and/or metastatic HCC who have progressed on 1 prior systemic treatment, which must have included anti-programmed cell death 1 (PD-1)/anti-PD-L1 therapy. Patients will receive atezolizumab plus bevacizumab therapy combined with RP2.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Pennsylvania, Abramson Cancer Center Philadelphia, PA

The West Clinic Germantown, TN

University of Louisville Louisville, KY

UC San Diego Moores Cancer Center La Jolla, CA

More Trial Locations

Who Is Running the Clinical Trial?

Replimune Inc.

Lead Sponsor

Trials

16

Recruited

1,700+

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

Findings from Research

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 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]

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]

In a real-world study of 61 patients with hepatocellular carcinoma (HCC), the combination of atezolizumab and bevacizumab showed a median progression-free survival (PFS) of 5.4 months and an objective response rate (ORR) of 35.3%.

The treatment was found to be safe, with a high incidence of adverse events (98.0%), primarily hepatic disorders, but it remained effective even in patients with prior treatment histories or varying liver function as indicated by albumin-bilirubin (ALBI) grades.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice. Iwamoto, H., Shimose, S., Noda, Y., et al.[2021]

In a study of 49 patients with advanced hepatocellular carcinoma (HCC) who progressed on atezolizumab-bevacizumab, second-line treatment with multikinase inhibitors (MKIs) like sorafenib and lenvatinib showed a median progression-free survival of 3.4 months and an overall survival of 14.7 months, indicating that these therapies can be effective after initial treatment failure.

Lenvatinib demonstrated a significantly longer median progression-free survival compared to sorafenib (6.1 vs. 2.5 months), although overall survival rates were similar between the two treatments, suggesting that while lenvatinib may delay disease progression, both treatments are viable options with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study. Yoo, C., Kim, JH., Ryu, MH., et al.[2022]

In a study of 216 patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (AtezoBev), the treatment demonstrated a median overall survival of 14.9 months and a median progression-free survival of 6.8 months, indicating its efficacy in a real-world clinical setting.

Patients with impaired liver function (Child-Pugh class B) experienced similar rates of treatment-related adverse events compared to those with better liver function (Child-Pugh class A), suggesting that AtezoBev is tolerable and may be a viable option for this underserved population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. D'Alessio, A., Fulgenzi, CAM., Nishida, N., 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]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

Atezolizumab and bevacizumab as first line therapy in advanced hepatocellular carcinoma: Practical considerations in routine clinical practice. [2021]

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

Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. [2023]

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

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Hepatic Events and Viral Kinetics in Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab. [2023]

10. 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]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study. [2022]

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

Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. [2023]

13. Greece pubmed.ncbi.nlm.nih.gov

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