Durvalumab + Tremelimumab + Radiation for Liver Cancer

Recruiting at 1 trial location

Overseen By Theodore Hong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disease, Organ transplant, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 8 months

70 Participants Needed

Trial Summary

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 use immunosuppressive medications within 28 days before starting the trial, except for certain corticosteroids and premedications for hypersensitivity reactions. If you have hepatitis B, you must continue antiviral medication for viral suppression.

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

The combination of Tremelimumab and Durvalumab has been approved for treating unresectable hepatocellular carcinoma (a type of liver cancer) based on the HIMALAYA study, which showed improved overall survival compared to another treatment, sorafenib. The median overall survival was 16.4 months with the combination, compared to 13.8 months with sorafenib. ^{1 2 3 4 5}

Is the combination of Durvalumab and Tremelimumab generally safe for humans?

The combination of Durvalumab and Tremelimumab has been studied in various cancers and is generally considered to have a tolerable safety profile, though it can cause side effects like rash, fatigue, diarrhea, and abdominal pain. In some studies, serious side effects occurred in about 32.6% of patients, which is higher than when using Durvalumab alone. ^{1 2 3 4 6}

How is the drug combination of Durvalumab and Tremelimumab unique for liver cancer treatment?

The combination of Durvalumab and Tremelimumab is unique for liver cancer treatment because it involves two immune checkpoint inhibitors that work together to enhance the body's immune response against cancer cells, and it has shown improved overall survival compared to the standard treatment, sorafenib, in patients with unresectable hepatocellular carcinoma. ^{1 2 3 4 7}

What is the purpose of this trial?

This research study is studying a combination of drugs as a possible treatment for Hepatocellular Carcinoma or Biliary Tract Cancer. The interventions involved in this study are: * Durvalumab * Tremelimumab * Radiation Therapy

Research Team

Theodore S Hong, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Adults with advanced liver or biliary tract cancer, who haven't had certain treatments and are not pregnant. They must have good organ function, no prior immunotherapy, and be able to follow the study plan. Those with hepatitis B or C need controlled infection levels.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

I have never received immunotherapy.

I have hepatitis C confirmed by a specific blood test.

Exclusion Criteria

I have moderate to severe nerve pain or damage, and need to discuss this with the study doctor.

I have not had major surgery in the last 28 days.

I have had a solid organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab and Tremelimumab via IV infusion every 28 days for up to 4 cycles, with radiation therapy during cycle 2. Durvalumab monotherapy continues every 4 weeks starting on Week 16 for up to 8 months.

8 months

IV infusion every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after the last dose

Long-term follow-up

Participants are monitored for disease progression and survival

Approximately 7 years

Treatment Details

Interventions

• Durvalumab
• Radiation Therapy
• Tremelimumab

Trial Overview The trial is testing a combination of two drugs (Durvalumab and Tremelimumab) along with radiation therapy as a potential treatment for Hepatocellular Carcinoma or Biliary Tract Cancer.

Participant Groups

Group I: Tremelimumab + Durvalumab + Radiation Experimental Treatment 3 Interventions

* Durvalumab via IV infusion every 28 days for up to 4 doses/cycles * Tremelimumab via IV infusion every 28 days for up to 4 doses/cycles, and then continue durvalumab monotherapy every 4 weeks starting on Week 16 for up to 8 months. * Radiation therapy will only be given during cycle 2

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

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

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

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.

This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Filippi, AR., Dziadziuszko, R., García Campelo, MR., et al.[2022]

In a safety run-in phase of the DURIGAST PRODIGE 59 study involving 11 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, 63.6% experienced significant adverse events, primarily neutropenia, indicating a notable safety concern with the treatment combination.

The combination of FOLFIRI with Durvalumab and/or Tremelimumab showed an expected safety profile, allowing progression to the randomized phase II study, although careful monitoring for serious adverse events is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. Evrard, C., Aparicio, T., Soularue, E., et al.[2022]

Radioembolization with yttrium-90 resin microspheres can be safely combined with full doses of durvalumab and tremelimumab in patients with metastatic colorectal cancer, with no significant treatment-related toxicities observed.

However, this combination did not lead to any immune responses in the tumors, indicating that yttrium-90 does not convert 'cold tumors' into 'inflamed' tumors that could respond to immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Feasibility Study of Yttrium-90 Liver Radioembolization Followed by Durvalumab and Tremelimumab in Patients with Microsatellite Stable Colorectal Cancer Liver Metastases. Wang, C., Park, J., Ouyang, C., et al.[2021]

References

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

Tremelimumab: First Approval. [2023]

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

FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]

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

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]

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

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A Pilot Feasibility Study of Yttrium-90 Liver Radioembolization Followed by Durvalumab and Tremelimumab in Patients with Microsatellite Stable Colorectal Cancer Liver Metastases. [2021]