760 Participants Needed

Immunotherapy + TACE +/- Lenvatinib for Liver Cancer

(EMERALD-3 Trial)

Recruiting at 157 trial locations
AC
Overseen ByAstraZeneca Clinical Study Information Center
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: AstraZeneca
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Do I have to stop taking my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Do I need to stop my current medications for this trial?

The trial information does not specify if 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 idea that Immunotherapy + TACE +/- Lenvatinib for Liver Cancer is an effective treatment?

The available research shows that the combination of tremelimumab and durvalumab, which are part of the immunotherapy treatment, has been approved for treating liver cancer. In a study called HIMALAYA, this combination was shown to help patients live longer compared to another drug called sorafenib. Specifically, patients lived for about 16.4 months on average with the combination treatment, compared to 13.8 months with sorafenib. This suggests that the immunotherapy combination is more effective than some existing treatments for liver cancer.12345

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

The combination of Durvalumab and Tremelimumab has been shown to improve overall survival in patients with unresectable hepatocellular carcinoma (a type of liver cancer) compared to the drug sorafenib, as demonstrated in the HIMALAYA study. This combination was approved by the FDA based on these results, indicating its effectiveness in treating this type of liver cancer.12345

What safety data exists for the treatment of liver cancer with Immunotherapy + TACE +/- Lenvatinib?

The provided research does not contain relevant safety data for the treatment of liver cancer with Immunotherapy + TACE +/- Lenvatinib. The studies focus on the safety and efficacy of teriflunomide and other treatments for multiple sclerosis, not the treatments in question for liver cancer.678910

Is the drug combination of Durvalumab, Lenvatinib, and Tremelimumab promising for liver cancer?

Yes, the combination of these drugs shows promise for treating liver cancer. Studies suggest that using Lenvatinib with other treatments like Durvalumab and Tremelimumab can be effective, especially for cases where surgery isn't an option. This combination may improve the treatment's effectiveness against the cancer.1112131415

How is the treatment with Durvalumab, Lenvatinib, and Tremelimumab for liver cancer different from other treatments?

This treatment combines immunotherapy (using the body's immune system to fight cancer) with a drug called Lenvatinib and a procedure called TACE (which blocks blood supply to the tumor), offering a unique approach for liver cancer that cannot be removed by surgery. It is different because it combines multiple methods to potentially enhance effectiveness against the cancer.1112131415

What is the purpose of this trial?

A global study to evaluate transarterial chemoembolization (TACE) in combination with durvalumab, tremelimumab and lenvatinib therapy in patients with locoregional hepatocellular carcinoma

Eligibility Criteria

This trial is for adults with hepatocellular carcinoma (a type of liver cancer) that can't be removed by surgery but can be treated with TACE. Participants should have no cancer outside the liver, an ECOG performance status of 0 or 1 indicating they are fully active or restricted in physically strenuous activity only, and a Child Pugh score class A showing mild liver disease.

Inclusion Criteria

My cancer has not spread outside my liver.
My liver function is good.
I am fully active or restricted in physically strenuous activity but can do light work.
See 3 more

Exclusion Criteria

I have had serious heart problems like heart failure, chest pain, or irregular heartbeat.
I am co-infected with both Hepatitis B and D.
Major portal vein thrombosis visible on baseline imaging
See 2 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tremelimumab, Durvalumab, and Lenvatinib in combination with Transarterial Chemoembolization (TACE) or TACE alone

Approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Durvalumab
  • Lenvatinib
  • Transarterial Chemoembolization (TACE)
  • Tremelimumab
Trial Overview The study tests if combining TACE with durvalumab and tremelimumab, with or without lenvatinib, improves outcomes in patients with locoregional HCC. It's a global study assessing the effectiveness and safety of these therapies when used together.
Participant Groups
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm BExperimental Treatment3 Interventions
Tremelimumab and Durvalumab in combination with Transarterial Chemoemobolization (TACE)
Group II: Arm AExperimental Treatment4 Interventions
Tremelimumab, Durvalumab and Lenvatinib in combination with Transarterial Chemoembolization (TACE)
Group III: Arm CActive Control1 Intervention
Transarterial Chemoembolization (TACE)

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

🇪🇺
Approved in European Union as Imfinzi for:
  • Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸
Approved in United States as Imfinzi for:
  • Extensive-stage small cell lung cancer (ES-SCLC)
  • Limited-stage small cell lung cancer (LS-SCLC)
  • Locally advanced or metastatic urothelial carcinoma
🇯🇵
Approved in Japan as Imfinzi for:
  • Not specified in provided sources

Find a Clinic Near You

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.
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]
Tremelimumab, a CTLA-4 blocking antibody, was approved in the USA in October 2022 for treating unresectable hepatocellular carcinoma (uHCC) in combination with durvalumab, marking a significant advancement in cancer therapy.
In November 2022, tremelimumab was also approved for metastatic non-small cell lung cancer (mNSCLC) when combined with durvalumab and platinum-based chemotherapy, indicating its broad potential in treating various malignant tumors.
Tremelimumab: First Approval.Keam, SJ.[2023]
The FDA approved tremelimumab in combination with durvalumab for treating unresectable hepatocellular carcinoma based on the HIMALAYA study, which showed a significant improvement in overall survival (OS) compared to sorafenib, with a median OS of 16.4 months versus 13.8 months.
Common adverse reactions in patients receiving the combination treatment included rash, fatigue, diarrhea, and abdominal pain, occurring in 20% or more of patients, indicating the need for monitoring during treatment.
FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma.Patel, TH., Brewer, JR., Fan, J., et al.[2023]

References

A multicenter, phase Ib/II, open-label study of tivozanib with durvalumab in advanced hepatocellular carcinoma (DEDUCTIVE). [2023]
Tremelimumab: First Approval. [2023]
FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma. [2023]
Durvalumab: First Global Approval. [2022]
New treatment paradigm with systemic therapy in intermediate-stage hepatocellular carcinoma. [2023]
Teriflunomide. [2021]
7.Russia (Federation)pubmed.ncbi.nlm.nih.gov
[Efficacy, tolerability and safety of the treatment with teberif: the results of a 2-year randomized clinical trial of treatment naïve patients with remitting multiple sclerosis, who have not received DMT, after switching from other interferon β-1a]. [2019]
Comparative effectiveness of teriflunomide and dimethyl fumarate: A nationwide cohort study. [2021]
Tolerability and discontinuation rates in teriflunomide-treated patients. A real-world clinical experience. [2021]
Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. [2022]
Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study. [2022]
Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib following Immunotherapy: A Real World Evidence Study. [2023]
13.United Statespubmed.ncbi.nlm.nih.gov
Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma. [2023]
The combination treatment strategy of lenvatinib for hepatocellular carcinoma: a real-world study. [2023]
Objective Response by mRECIST to Initial Lenvatinib Therapy Is an Independent Factor Contributing to Deep Response in Hepatocellular Carcinoma Treated with Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy. [2022]
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