Tremelimumab + Durvalumab for Liver Cancer

Overseen By Epp Goodwin

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center at San Antonio

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Substance abuse, Autoimmune disorders, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: Variable (until disease progression or unacceptable toxicity)

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, Tremelimumab and Durvalumab, to determine their safety and effectiveness for people with advanced liver cancer. The focus is on individuals who have not yet received treatment for their liver cancer, particularly those with liver issues from cirrhosis and hepatitis. For those with advanced liver cancer whose doctors have not recommended surgery or other therapies, this trial might be suitable. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of participants.

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 use any immunosuppressive medication within 14 days before starting the trial drugs, except for certain low-dose steroids and specific types of steroid treatments.

Is there any evidence suggesting that Tremelimumab and Durvalumab are likely to be safe for humans?

Research has shown that the combination of tremelimumab and durvalumab has been tested for treating advanced liver cancer. These studies found that most patients can handle the treatment well. In a previous study with liver cancer patients, this treatment helped them live longer compared to other treatments.

Safety information from these studies indicated that most side effects were manageable. Common side effects included fatigue and reduced appetite, typical for cancer treatments. Serious side effects were less common and similar to those seen with other cancer therapies.

This treatment combination is already approved for other conditions, providing some confidence in its safety. Overall, evidence suggests that tremelimumab and durvalumab can be tolerated by patients with advanced liver cancer. However, discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver cancer?

Researchers are excited about Tremelimumab and Durvalumab for liver cancer because they offer a fresh approach compared to the current standard treatments like sorafenib or lenvatinib. Unlike traditional treatments that mainly target cancer cell growth, Tremelimumab and Durvalumab work by harnessing the immune system to fight the cancer. Tremelimumab blocks a protein called CTLA-4, and Durvalumab targets PD-L1, both helping the immune system recognize and attack cancer cells more effectively. This dual mechanism has the potential to improve outcomes for patients by offering a more targeted approach to treatment.

What evidence suggests that Tremelimumab and Durvalumab might be an effective treatment for liver cancer?

Research has shown that using Tremelimumab and Durvalumab together yields promising results for treating advanced liver cancer. In studies, patients receiving this combination lived an average of 16.4 months, compared to 13.8 months with sorafenib. One study found that one in five patients survived for five years on this treatment. In this trial, participants will receive Tremelimumab and Durvalumab in the Stride (Single T Regular Interval D) Arm. Overall, these findings suggest that Tremelimumab and Durvalumab could extend the lives of people with advanced liver cancer. ^{3 4 5 6 7}

Who Is on the Research Team?

Sukeshi P Arora, MD

Principal Investigator

The University of Texas Health Science Center at San Antonio

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver cancer or hepatocellular carcinoma who are fit for first-line treatment. It's especially aimed at those often underrepresented in trials, like racial/ethnic minorities and individuals from low socioeconomic backgrounds. Participants must have a specific level of liver impairment known as Child-Pugh-B cirrhosis.

Inclusion Criteria

Must have a life expectancy of at least 12 weeks

I am willing and able to follow the study's treatment and visit schedule.

I weigh more than 30 kilograms.

Exclusion Criteria

I don't have any other cancers that could affect this treatment's safety or results.

I have had treatment for advanced liver cancer before.

Active substance abuse or alcohol abuse at the time of consent or enrollment, which in the opinion of the treating physician would interfere with the safety of the patient and/or adherence to the study protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Priming dose of tremelimumab 300 mg IV once with durvalumab 1500 mg IV on Day 1 of each 4-week cycle. Patients will stay on study treatment until evidence of disease progression, unacceptable toxicity, or death.

Variable (until disease progression or unacceptable toxicity)

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. A repeat CT/MRI scan will be performed after 2 cycles to evaluate response. Serum tumor marker AFP and CT/MRI scans will be repeated at least every 2 cycles.

Up to 1 year

Every 8 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tremelimumab and Durvalumab

Trial Overview The study tests the combination of two drugs, Tremelimumab and Durvalumab (T300+D), on patients with advanced liver cancer to see if it's safe and can be tolerated. This phase II trial does not compare against other treatments but aims to gather safety data specifically in a diverse patient population.

How Is the Trial Designed?

Group I: Stride (Single T Regular Interval D) Arm Experimental Treatment 2 Interventions

Tremelimumab dosed once at the beginning of the first cycle, 300mg IV infusion and Durvalumab 1500mg IV dosed with the first dose of Tremelimumab and then once per cycle (every 4 weeks)

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

Approved in United States as Imjudo and Imfinzi for:

• Unresectable hepatocellular carcinoma
• Metastatic non-small cell lung cancer

Approved in European Union as Imjudo and Imfinzi for:

• Advanced liver cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

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

Published Research Related to This Trial

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]

In the phase III HIMALAYA trial, patients with inoperable hepatocellular carcinoma who received a single dose of tremelimumab combined with monthly durvalumab showed improved overall survival compared to those treated with sorafenib.

This suggests that the combination therapy may be a more effective first-line treatment option for this type of liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Immunotherapy Makes Strides against HCC. [2022]

This phase II study aims to evaluate the effectiveness of combining durvalumab and tremelimumab with neoadjuvant chemotherapy in improving progression-free survival (PFS) in patients with advanced-stage ovarian cancer, specifically those with stage IIIC/IV epithelial ovarian cancer.

The study will involve 24 patients and will assess immune biomarkers and changes in the tumor microenvironment through serial biopsies, with the primary goal of achieving a 12-month PFS rate, while also monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D. Lee, JY., Kim, JW., Lim, MC., et al.[2020]

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 tremelimumab and durvalumab (T300 + D) showed the highest overall survival rate (18.7 months) and objective response rate (24.0%) among patients with unresectable hepatocellular carcinoma, indicating its potential as an effective treatment option.

All treatment regimens were generally well-tolerated, but T300 + D had the most favorable safety profile, with a significant association between early CD8+ lymphocyte expansion and treatment response, suggesting a promising mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. Kelley, RK., Sangro, B., Harris, W., et al.[2022]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10841291/

FDA Approval Summary: Tremelimumab in combination ... The median OS was 16.4 months (95% CI, 14.2 to 19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3 to 16.1) with sorafenib.

2. 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 ...

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

Tremelimumab plus Durvalumab in Unresectable ... Conclusions. STRIDE significantly improved overall survival versus sorafenib. Durvalumab monotherapy was noninferior to sorafenib for patients ...

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

5-YEAR FOLLOW-UP RESULTS - IN uHCC Find the 5-year clinical trial results for IMFINZI® (durvalumab) + IMJUDO® (tremelimumab-actl), a treatment for adults diagnosed with unresectable ...

5. astrazeneca-us.com astrazeneca-us.com/media/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® (durvalumab) plus IMJUDO® (tremelimumab-actl ... AstraZeneca's IMFINZI (durvalumab) plus IMJUDO (tremelimumab-actl) demonstrated a sustained, clinically meaningful overall survival (OS) benefit at five years.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK599983/

Tremelimumab (Imjudo) in Combination With Durvalumab ... The OS rate at 36 months was 30.7% (95% CI, 25.8% to 35.7%) in the tremelimumab in combination with durvalumab group and 20.2% (95% CI, 15.8% to 25.1%) in the ...

7. imfinzihcp.com imfinzihcp.com/hcc/unresectable/safety.html

Safety Profile of IMFINZI® (durvalumab) & IMJUDO® ... Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase 3 HIMALAYA ...