Durvalumab + Bevacizumab for Liver Cancer

(EMERALD-2 Trial)

Not currently recruiting at 232 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for liver cancer, focusing on individuals at high risk of recurrence. Researchers aim to evaluate the effectiveness of durvalumab (an immunotherapy) alone or combined with bevacizumab (also known as Avastin, a targeted therapy), compared to a placebo (a substance with no active drug). Individuals who recently underwent surgery or another successful liver cancer treatment and are currently cancer-free might qualify for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking advancements in liver cancer treatment.

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.

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

Research has shown that the combination of durvalumab and bevacizumab is generally well-tolerated. In another study involving patients with liver cancer that cannot be surgically removed, this combination did not introduce any new side effects, meaning no unexpected or unusual side effects occurred.

Earlier studies indicate that durvalumab alone also has a manageable safety profile, with side effects typically being predictable and manageable by doctors. However, liver problems were more common when durvalumab was combined with certain chemotherapy drugs, which is not the case here.

Overall, past research suggests that both treatments are safe, providing reassurance to patients about potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Durvalumab and Bevacizumab for liver cancer because it represents a novel approach to treatment. Unlike traditional therapies such as Sorafenib and Lenvatinib, which primarily inhibit tumor growth by blocking certain cell signaling pathways, Durvalumab is an immunotherapy that works by unleashing the immune system to attack cancer cells, specifically by blocking the PD-L1 protein. Bevacizumab complements this by targeting and inhibiting the formation of blood vessels that tumors need to grow. This dual-action approach not only potentially boosts the immune response but also cuts off the tumor's blood supply, offering a promising new strategy for tackling liver cancer.

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

Research has shown that using durvalumab and bevacizumab together holds promise for treating liver cancer. In earlier studies, this combination reduced the risk of cancer progression or death by 23% compared to other treatments. In this trial, participants in Arm A will receive this combination. Patients on this combination also experienced longer periods before their cancer worsened. Meanwhile, participants in Arm B will receive durvalumab alone, which has also proven effective, with 53.3% of patients seeing their cancer shrink or disappear, and 90% having their disease under control. These results suggest that both treatments could be good options for liver cancer. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/study/NCT05027425

Study Details | NCT05027425 | Durvalumab (MEDI4736) ... Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.TPS630

Phase II trial of durvalumab (MEDI4736) with/without ... Phase II trial of durvalumab (MEDI4736) with/without tremelimumab for advanced hepatocellular carcinoma after palliative hypofractionated radiotherapy.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6738201/

Immuno-Oncology Therapy for Hepatocellular Carcinoma Although only 30 patients were evaluated for safety and efficacy, the ORR per RECIST 1.1 was 53.3%, the disease control rate was 90.0%, and 6.7% ...

4. imfinzihcp.com imfinzihcp.com/hcc/unresectable/efficacy.html

Efficacy Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase 3 HIMALAYA ...

5. imfinzi.com imfinzi.com/hepatocellular-carcinoma/about-imfinzi/clinical-trial-results.html

5-YEAR FOLLOW-UP RESULTS - IN uHCC A clinical trial compared 2 groups of people with uHCC whose cancer wasn't previously treated. The main goal of this study was to measure overall survival, ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/520275

Study of Tremelimumab and Durvalumab ... - Carebox Connect It can be used to predict the prognosis of patients with liver cirrhosis and hepatocellular carcinoma, and has been shown to be more accurate ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06911255

Safety and Efficacy of Tremelimumab+Durvalumab ... The purpose of this clinical trial is to evaluate the safety and efficacy of tremelimumab + durvalumab administered concurrently with transarterial ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9637844/

Liver injury during durvalumab-based immunotherapy is ... Durvalumab given in combination with cytotoxic chemotherapy resulted in the highest rate of liver injury (71.4%% vs. 29.7%) compared to when it was given alone ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05027425

Study Details | NCT05027425 | Durvalumab (MEDI4736) ... Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.67.9761

Safety and Efficacy of Durvalumab (MEDI4736), an Anti– ... Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1–positive patients with UBC, many of whom were heavily ...