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

Trial Summary

What is the purpose of this trial?

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 combination with durvalumab and tremelimumab following front-line treatment in patients with advanced stage BTC.

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.

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

Research shows that Durvalumab, when combined with gemcitabine and cisplatin, significantly improves survival in advanced biliary tract cancer. Additionally, Tremelimumab has shown potential benefits when used with other treatments, like microwave ablation, in similar patients. ^{1 2 3 4 5}

Is the combination of Peptide Vaccine, Durvalumab, and Tremelimumab safe for humans?

The combination of durvalumab and tremelimumab has been studied for safety in various cancers, including biliary tract cancer and hepatocellular carcinoma. Common side effects reported in these studies include rash, fatigue, diarrhea, itching, muscle pain, and abdominal pain. These treatments have been approved for use in certain cancers, indicating a recognized safety profile. ^{1 2 5 6 7}

How does the peptide vaccine with durvalumab and tremelimumab treatment differ from other treatments for biliary tract cancer?

This treatment is unique because it combines a peptide vaccine with two immunotherapy drugs, durvalumab and tremelimumab, which work by helping the immune system recognize and attack cancer cells. This approach is different from standard chemotherapy and aims to enhance the body's natural defenses against cancer. ^{1 2 3 4 8}

Research Team

Marina Baretti, MD

Principal Investigator

SKCCC Johns Hopkins Medical Institution

Eligibility Criteria

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

I agree to have a biopsy of my cancer before and during treatment.

Exclusion Criteria

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)

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

I have an autoimmune disease that needed treatment in the last 5 years.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. Netherlands 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. [2023]

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

Tremelimumab in Combination With Microwave Ablation in Patients With Refractory Biliary Tract Cancer. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Advanced Biliary Tract Cancer. [2023]

5. United States 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. [2022]

6. 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]

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

Tremelimumab: First Approval. [2023]

8. Japan pubmed.ncbi.nlm.nih.gov

Possibility of immunotherapy for biliary tract cancer: how do we prove efficacy? Introduction to a current ongoing phase I and randomized phase II study to evaluate the efficacy and safety of adding Wilms tumor 1 peptide vaccine to gemcitabine and cisplatin for the treatment of advanced biliary tract cancer (WT-BT trial). [2022]