Tremelimumab + Durvalumab for Liver Cancer

Overseen By Mehmet Akce, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mehmet Akce

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Heart failure, Autoimmune disorders, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs, including Tremelimumab and Durvalumab, to evaluate their effectiveness in treating a specific type of liver cancer called combined hepatocellular-cholangiocarcinoma (cHCC-CCA), which is advanced and inoperable. The goal is to determine if this treatment can help control the cancer's growth. Suitable participants have been diagnosed with this type of liver cancer and cannot undergo surgery for removal. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take other cancer treatments or immunosuppressive medications while participating. It's best to discuss your current medications with the study team.

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

Research has shown that the combination of Tremelimumab and Durvalumab is generally well-tolerated by people with liver cancer. While some side effects occur, they are usually manageable. Common side effects include fatigue, skin rash, and changes in liver function tests, but serious reactions are less common.

Gemcitabine and Cisplatin, also part of the treatment, have been used in cancer care for many years. These drugs can cause side effects like nausea, vomiting, and low blood cell counts, but doctors typically monitor and manage these.

Overall, the treatments in this trial have been studied before and are considered reasonably safe, with side effects that doctors are familiar with managing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tremelimumab and Durvalumab for liver cancer because they offer a novel approach by harnessing the immune system to fight cancer cells. Unlike traditional chemotherapy, which directly targets and kills cancer cells, these drugs are immune checkpoint inhibitors. They work by blocking proteins that prevent the immune system from attacking cancer, potentially enhancing the body's natural defenses to fight the tumor more effectively. Additionally, the combination with Gemcitabine and Cisplatin might offer a synergistic effect, potentially improving outcomes compared to standard treatments alone. This innovative approach could provide new hope for patients who have limited options with existing therapies.

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

Research has shown that using Tremelimumab and Durvalumab together holds potential for treating advanced liver cancer. In earlier studies, this drug combination helped many patients by shrinking tumors or halting their growth. Specifically, one study found that one in five patients lived for five years with this treatment, marking a significant improvement for advanced liver cancer. This trial will evaluate the combination of Tremelimumab and Durvalumab with Gemcitabine and Cisplatin to determine its effectiveness in liver cancer, offering hope for better outcomes. ^{1 6 7 8 9}

Who Is on the Research Team?

Mehmet Akce, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver cancer called combined hepatocellular-cholangiocarcinoma that can't be removed by surgery. Participants must have a good performance status, meaning they're able to carry out daily activities with minimal assistance. They need proper organ and marrow function, weigh over 30 kg, and have a life expectancy of at least 12 weeks.

Inclusion Criteria

Must have life expectancy ≥ 12 weeks.

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations. Informed written consent must be ≤ 28 days prior to registration.

Body weight > 30 kg.

Exclusion Criteria

Participation in another clinical study with an investigational product ≤ 28 days prior to registration unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.

Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.

Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and Cisplatin. Cycles 1-8 are in 3-week intervals, and Cycles 9+ are in 4-week intervals.

Up to 24 months

Visits every 3 weeks for Cycles 1-8, then every 4 weeks for Cycles 9+

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Disease assessments every 9 weeks until the end of Cycle 9, then every 8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Durvalumab
• Gemcitabine
• Tremelimumab

Trial Overview The study tests Tremelimumab once plus Durvalumab regularly with Gemcitabine and Cisplatin chemotherapy in specific intervals for up to 24 months or until the disease progresses or side effects become too severe. The goal is to see how well this combination works against this type of liver cancer.

How Is the Trial Designed?

Group I: Single Tremelimumab with Regular Interval Durvalumab plus Gemcitabine and Cisplatin Experimental Treatment 4 Interventions

Cycles 1 through 8 will be in 3-week intervals and Cycles 9+ will be in 4-week intervals. Tremelimumab is administered at 300mg intravenously once at Cycle 1. Durvalumab is administered at 1500mg intravenously every 3 weeks for Cycles 1-8, then every 4 weeks for Cycles 9+. Gemcitabine is administered at 1000mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only. Cisplatin is administered at 25mg/m\^2 intravenously on Day 1 and Day 8 of Cycles 1-8 only.

Who Is Running the Clinical Trial?

Mehmet Akce

Lead Sponsor

Trials

2

Recruited

70+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

AstraZeneca

Industry 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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12401040/

Efficacy of Durvalumab‐Tremelimumab Treatment in ... Systemic therapy with immune checkpoint inhibitors for advanced hepatocellular carcinoma (HCC) treatment has demonstrated high response rates.

2. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2100070

Tremelimumab plus Durvalumab in Unresectable ... The primary outcome was overall survival, defined as time from date of randomization until death from any cause, for STRIDE versus sorafenib.

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2824%2900049-8/fulltext

Four-year overall survival update from the phase III ... The survival rates at 18, 24, 36, and 48 months were 47.4%, 39.6%, 24.7%, and 19.3%, respectively, in the durvalumab arm. OS in the prespecified ...

4. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2024/imfinzi-plus-imjudo-demonstrated-unprecedented-overall-survival-alc-with-one-in-five-patients-surviving-five-years-himalaya-phase-iii-trial.html

Imfinzi plus Imjudo demonstrated unprecedented overall ... Imfinzi plus Imjudo demonstrated unprecedented overall survival in advanced liver cancer with one in five patients surviving five years in ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01462

Patient-Reported Outcomes From the Phase III HIMALAYA ... Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11589085/

Early Clinical Outcomes of Durvalumab Plus ... Durvalumab plus tremelimumab may be effective and safe for unresectable hepatocellular carcinoma, even in patients who receive it as a later- ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4122

Sequential or up-front triple combination with durvalumab ... The MONTBLANC trial evaluates the efficacy and safety of combined durva, treme and bev in patients (pts) with aHCC.

8. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1657398/full

A real-world drug safety surveillance study from the FAERS ... Overall, this study characterizes the adverse event profile of durvalumab plus tremelimumab in patients with HCC using the FAERS database, providing key ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06911255

NCT06911255 | Safety and Efficacy of Tremelimumab ... The purpose of this clinical trial is to evaluate the safety and efficacy of tremelimumab + durvalumab administered concurrently with transarterial ...