Durvalumab + Bevacizumab for Liver Cancer

(EMERALD-2 Trial)

Recruiting at 180 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Disqualifiers: Metastasis, Macrovascular invasion, Hepatic encephalopathy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 3

Duration: Up to 49 months

908 Participants Needed

Trial Summary

What is the purpose of this trial?

A global study to assess the efficacy and safety of durvalumab in combination with bevacizumab or durvalumab alone in patients with hepatocellular carcinoma who are at high risk of recurrence.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Durvalumab, a drug that helps the immune system fight cancer, has shown benefits in prolonging survival in liver cancer patients. Bevacizumab, when combined with another similar drug, has been used effectively in treating advanced liver cancer. This suggests that the combination of Durvalumab and Bevacizumab could be promising for liver cancer treatment. ^{1 2 3 4 5}

Is the combination of Durvalumab and Bevacizumab safe for humans?

Durvalumab has been shown to have a manageable safety profile in various cancers, including lung cancer, when used alone or with other treatments. Bevacizumab, when combined with atezolizumab, has been studied for safety in liver cancer patients, showing a meaningful survival benefit. While specific safety data for the combination of Durvalumab and Bevacizumab in liver cancer is not available, both drugs have been used safely in other combinations. ^{1 2 3 4 6}

What makes the drug combination of Durvalumab and Bevacizumab unique for liver cancer?

The combination of Durvalumab, an immune checkpoint inhibitor that blocks PD-L1, and Bevacizumab, which inhibits blood vessel growth in tumors, offers a novel approach by targeting both the immune system and tumor blood supply, potentially enhancing treatment effectiveness for liver cancer. ^{1 2 3 4 7}

Research Team

Jia Fan, MD

Principal Investigator

Liver Cancer Institute Zhongshan Hospital, Fudan University

Jennifer Knox, MD

Principal Investigator

Solid Tumor Medical Oncology Princess Margaret Cancer Centre

Eligibility Criteria

This trial is for patients with a specific liver cancer (HCC) who've had successful curative therapy like surgery or ablation and are currently disease-free. They should be in good physical condition (ECOG 0-1), have a stable liver function score (Child-Pugh 5 or 6), and their organs must work well. People with certain types of HCC, evidence of spread, previous hepatic encephalopathy, portal vein thrombosis, co-infections, those awaiting liver transplants, or at risk of bleeding varices can't join.

Inclusion Criteria

I have been diagnosed with liver cancer and completed curative therapy.

My organs and bone marrow are working well.

I am fully active or can carry out light work.

Exclusion Criteria

My scans show cancer has spread or is affecting my blood vessels.

Those on a waiting list for liver transplantation

Active co-infection with HBV and HDV

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab monotherapy or in combination with bevacizumab as adjuvant therapy

Up to 49 months

Every 3 weeks (Q3W)

Follow-up

Participants are monitored for recurrence-free survival and overall survival

Up to 49 months

Treatment Details

Interventions

• Bevacizumab
• Durvalumab

Trial Overview The study tests the effectiveness and safety of Durvalumab alone or combined with Bevacizumab in preventing cancer recurrence in high-risk HCC patients after they've received curative treatment. Patients will be randomly assigned to receive either both drugs together, Durvalumab alone, or a placebo to compare outcomes.

Participant Groups

Group I: Arm B Experimental Treatment 2 Interventions

Durvalumab 1120 mg (Q3W) + bevacizumab placebo (Q3W)

Group II: Arm A Experimental Treatment 2 Interventions

Durvalumab 1120 mg (Q3W) + bevacizumab 15 mg/kg (Q3W)

Group III: Arm C Placebo Group 1 Intervention

Durvalumab placebo (Q3W) + bevacizumab placebo (Q3W)

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

The DEDUCTIVE trial is a phase Ib study evaluating the safety and tolerability of combining durvalumab, a PD-L1 inhibitor, with tivozanib, a VEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC).

Both durvalumab and tivozanib have shown effectiveness as single agents in HCC, but this trial aims to explore their concurrent use, particularly in treatment-naive patients and those who have progressed on other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, phase Ib/II, open-label study of tivozanib with durvalumab in advanced hepatocellular carcinoma (DEDUCTIVE). Mahmood, S., Li, D., Lee, A., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

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]

In a study of 112 patients receiving durvalumab for cancer treatment, 19% experienced liver injury, which was linked to higher rates of tumor progression and mortality, indicating that liver injury may be a significant concern in this patient population.

Among the liver injury cases, 29% were classified as probable drug-induced liver injury (DILI) related to durvalumab, but these cases were generally mild and self-limited, suggesting that while monitoring for liver injury is important, severe complications are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Swanson, LA., Kassab, I., Tsung, I., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

A multicenter, phase Ib/II, open-label study of tivozanib with durvalumab in advanced hepatocellular carcinoma (DEDUCTIVE). [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

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

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

5. Greece pubmed.ncbi.nlm.nih.gov

Initial Experience of Atezolizumab Plus Bevacizumab for Advanced Hepatocellular Carcinoma in Clinical Practice. [2022]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. [2023]