Peptide Vaccine + Durvalumab + Tremelimumab for Biliary Tract Cancer

Overseen By Joann Santmyer, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Steroids, Chemotherapy

Disqualifiers: Brain metastases, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 20 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced biliary tract cancer, which affects the bile ducts. Researchers aim to determine the safety and immune response effects of using a peptide vaccine with durvalumab and tremelimumab, both immune system boosters. Suitable candidates have biliary tract cancer previously treated with specific therapies and possess a tumor with a genetic change targeted by the vaccine. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have taken certain treatments like systemic steroids, chemotherapy, or investigational drugs within 2-4 weeks before starting the study. 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 durvalumab and tremelimumab has been tested in people with liver cancer. In these studies, most participants handled the treatments well. Common side effects included fatigue, loss of appetite, and skin rash, while more serious issues, such as liver problems, were less common.

Regarding the personalized mutant peptide vaccine (mBTCvax), specific information remains limited. As this trial is in an early stage, researchers focus on safety and monitor for side effects. Early trials primarily assess safety, so any major problems would likely be identified and addressed.

Overall, while the combination appears promising, researchers continue to carefully monitor safety. Participants should discuss any concerns with the trial team to understand the possible risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Durvalumab, Tremelimumab, and the mBTC vaccine for biliary tract cancer because it represents a novel approach to treatment. Unlike standard chemotherapy, which targets rapidly dividing cells, this combination leverages the body's immune system to fight cancer more effectively. Durvalumab and Tremelimumab are immune checkpoint inhibitors that help the immune system recognize and attack cancer cells, while the mBTC vaccine is designed to specifically target biliary tract cancer cells, potentially enhancing the immune response. This approach could lead to more precise and effective treatment outcomes, offering new hope for patients with this challenging condition.

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

Research shows that using durvalumab and tremelimumab together may help treat liver cancer that can't be removed with surgery. Studies have found that patients with this type of cancer live longer when treated with these drugs, with some living for five years or more. In this trial, participants will receive a combination of the personalized vaccine mBTCvax, durvalumab, and tremelimumab. Although data on mBTCvax remains limited, this vaccine is designed to help the immune system better target cancer cells. Early results suggest that combining the vaccine with durvalumab and tremelimumab might boost the immune response against biliary tract cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Marina Baretti, MD

Principal Investigator

SKCCC Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

This trial is for patients with advanced biliary tract or pancreatic cancer who have completed initial treatment. It's not suitable for those with certain medical conditions that could interfere with the study, or if they've had previous treatments that might affect the results.

Inclusion Criteria

Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test

Must have a life expectancy of at least 12 weeks

My body weight is over 30 kg.

Exclusion Criteria

Any other sound medical, psychiatric, and/or social reason as determined by the Investigator

Patient is at the time of signing informed consent a regular user (including 'recreational use') of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)

I have had a cancer-related blockage in my intestines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a personalized mutant peptide vaccine with poly-ICLC adjuvant (mBTCvax) in combination with durvalumab and tremelimumab

20 weeks

Regular visits for vaccination and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 months

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• mBTC vax
• Tremelimumab

Trial Overview The trial tests a personalized peptide vaccine (mBTCvax) combined with two immune-boosting drugs, Durvalumab and Tremelimumab, to see how safe it is and how well it triggers an immune response against cancer after first-line therapy.

How Is the Trial Designed?

Group I: Arm A - mBTCvax, Durvalumab and Tremelimumab Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

Private Philanthropic Funds

Collaborator

Trials

4

Recruited

150+

Private Philanthropic Funds

Collaborator

Published Research Related to This Trial

In a phase 2 study involving 128 patients with advanced biliary tract cancer, the combination of gemcitabine and cisplatin with the immunotherapy durvalumab (and tremelimumab for some) resulted in a promising objective response rate of 66%, indicating potential efficacy as a first-line treatment.

The treatment was generally safe, with the most common severe side effects being decreased neutrophil count and anemia, but no unexpected safety events or treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Oh, DY., Lee, KH., Lee, DW., 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.

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]

Durvalumab monotherapy and the combination of durvalumab with tremelimumab showed acceptable safety profiles, with grade ≥3 treatment-related adverse events occurring in 19.0% of patients with biliary tract cancer (BTC) and 25.0% with head and neck squamous cell carcinoma (HNSCC).

The combination therapy demonstrated a higher objective response rate (ORR) of 10.8% in BTC and 20.3% in esophageal squamous cell carcinoma (ESCC), indicating potential clinical benefit for patients with advanced cancers who had disease progression after prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and efficacy of durvalumab, either as monotherapy or in combination with tremelimumab, in patients from Asia with advanced biliary tract, esophageal, or head-and-neck cancer. Doki, Y., Ueno, M., Hsu, CH., et al.[2022]

In the safety run-in of the IMMUNOBIL PRODIGE 57 trial involving 20 patients, the combination of durvalumab and tremelimumab with paclitaxel resulted in a high rate of dose-limiting toxicities (50%), including serious anaphylactic reactions and other severe adverse events.

Due to the safety concerns raised by the combination therapy, the trial will proceed with only the durvalumab and tremelimumab combination, indicating that the addition of paclitaxel may not be safe for patients with advanced biliary tract carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. Boilève, A., Hilmi, M., Gougis, P., et al.[2021]

In the phase 3 TOPAZ-1 trial, the combination of durvalumab with gemcitabine and cisplatin significantly improved overall survival and progression-free survival in adults with advanced biliary tract cancer, compared to the placebo group.

Durvalumab's benefits were consistent across various patient factors, including tumor location and PD-L1 expression levels, and the treatment was found to be manageable in terms of tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Advanced Biliary Tract Cancer. Fung, S., Syed, YY.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06564623

Study Details | NCT06564623 | Targeting Driver ... The purpose of this study is to evaluate the safety and the immune response of personalized mutant peptide vaccine with poly-ICLC adjuvant (mBTCvax) in ...

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

Tremelimumab (Imjudo) in Combination With Durvalumab ... Imjudo in combination with Imfinzi should only be covered to treat adult patients who have confirmed liver cancer that cannot be removed by surgery, are ...

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

Efficacy and Clinical Trial Data for IMFINZI® (durvalumab) ... Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase 3 HIMALAYA ...

4. 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, ...

5. 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 ... AstraZeneca's Imfinzi (durvalumab) plus Imjudo (tremelimumab) demonstrated a sustained, clinically meaningful overall survival (OS) benefit at five years.

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

Safety Profile of IMFINZI® (durvalumab) & IMJUDO® ... Learn about the safety profile and the common adverse reactions for IMFINZI & IMJUDO in the HIMALAYA Study.