Targeting Driver Oncogenes With a Peptide Vaccine Plus Durvalumab and Tremelimumab for Patients With Biliary Tract Cancers (BTC)

A Pilot Study of Targeting Driver Oncogenes With a Peptide Vaccine Plus Durvalumab and Tremelimumab for Patients With Biliary Tract Cancers

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.

Study Overview

• Status: Recruiting
• Conditions: Biliary Tract Cancers
• Intervention / Treatment: Drug: mBTC vax [0.3 - 2.4 mg peptide + 0.5 mg Poly-ICLC (Hiltonol)]; Drug: Durvalumab; Drug: Tremelimumab

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • SKCCC Johns Hopkins Medical Institution
      • Contact: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
      • Principal Investigator: Marina Baretti, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Must have a histologically- or cytologically, proven biliary tract cancer (BTC) previously treated with gemcitabine/cisplatin/anti-PD(L)1 therapy.
• Must have evidence of radiological disease, must accept to have a tumor biopsy of an accessible lesion at baseline and on treatment.
• Must have sufficient archival tumor tissue for next-generation sequencing (NGS) and immune-phenotyping.
• Have a BTC containing at least one of the oncogenic mutation/alterations targeted by the vaccine.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Must have body weight of >30 kg.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• Patients with chronic or acute hepatitis B virus (HBV) or hepatitis C virus (HCV) infection must have disease controlled prior to enrollment.
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
• For both Women and Men, must use acceptable form of birth control while on study.
• Must have a life expectancy of at least 12 weeks.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Participation in another clinical study with an investigational product during the last 2 weeks.
• Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.

• Any of the following procedures or medications within 2 weeks prior to initiation of study treatment:

  • Systemic or topical steroids at immunosuppressive doses (> 10 mg/day of prednisone or equivalent). The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Palliative or adjuvant radiation or gamma knife radiosurgery.
  • Chemotherapy or checkpoint inhibitor targeting anti-Pd1/PD-L1.

• Within 4 weeks prior to initiation of study treatment:

  • Any investigational cytotoxic drug.
  • Any investigational device.
  • Non-oncology vaccines containing live virus.
  • Allergen hyposensitization therapy.
  • Growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin.
  • Major surgery.
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy.
• Patients with a history of prior treatment with anti-PD-1 and anti-PD-L1.
• History of severe hypersensitivity reaction to any monoclonal antibodies or related compounds or to any of its components.
• History of leptomeningeal carcinomatosis.
• Patient has a known history or evidence of brain metastases.
• Has an active known or suspected autoimmune disease or which has required systemic therapy in the last 5 years.
• Known history of interstitial lung disease or of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has a pulse oximetry < 92% on room air.
• Requires the use of home oxygen.
• Has a known history of Human Immunodeficiency Virus (HIV)/AIDS
• Has active co-infection with HBV (hepatitis B virus) and HCV (hepatitis C virus) or coinfected with HBV and hepatitis delta virus (HDV)
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who have been diagnosed with another cancer or myeloproliferative disorder in the past 5 years requiring systemic therapy or expected to require active therapy within the clinical study period.
• Has a diagnosis of immunodeficiency.
• Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.
• 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).
• Patient is unwilling or unable to follow the study schedule for any reason.
• Pregnant or breastfeeding.
• WOCBP and men with female partners (WOCBP) who are not willing to use contraception.
• Evidence of clinical ascites requiring paracentesis in the last 4 weeks.
• History of malignant bowel obstruction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm A - mBTCvax, Durvalumab and Tremelimumab

Drug: mBTC vax [0.3 - 2.4 mg peptide + 0.5 mg Poly-ICLC (Hiltonol)]; Patients will receive treatment on Day 1, 8, 15 and 22 of cycle 1 and on day 1 of remaining cycles (C2-C4) in Prime Phase. In the Boost Phase - every 2 cycles (8 weeks) beginning from C6D1.; Other Names: Peptide + Poly-ICLC (Hiltonol); Drug: Durvalumab; Patients will receive treatment on Day 1 of each cycle. Durvalumab (1500 mg) will be administered IV every 4 weeks in both the Prime and Boost Phase.; Other Names: IMFINZI®; Drug: Tremelimumab; Patients will receive treatment on C1D1. Tremelimumab (300 mg) will be administered IV as a single dose on Day 1 of Cycle 1.; Other Names: IMJUDO®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants experiencing grade 3 or above drug-related toxicities	When calculating the incidence of Adverse Events (AE), each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.	20 Months
Maximum percentage change in interferon-producing mutant-specific cluster of differentiation 8 (CD8) and cluster of differentiation 4 (CD4) T cells.	Evaluated by the maximal percent change in interferon-producing mutant-specific CD8 and CD4 T cells within 20 weeks post-vaccination compared to pre-vaccination baseline.	Baseline to 20 weeks post vaccination (baseline, 20 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the number of months from the date of first vaccine dose until the date of disease progression using RECIST 1.1 criteria or death due to any cause, whichever occurs first, for BTC patients. PFS will be censored at the date of the last scan for subjects without documentation of disease progression at the time of analysis. Per RECIST 1.1 criteria, Complete Response (CR) = disappearance of all target lesions, Partial Response (PR) is =>30percent decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20percent increase in sum of diameters of target lesions, Stable Disease (SD) is <30percent decrease or <20percent increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.	4 years
Overall Survival (OS)	OS will be defined as the number of months from the date of first vaccine dose until date of death due to any cause. OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at time of analysis. Estimation based on the Kaplan-Meier curve.	4 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: AstraZeneca; Private Philanthropic Funds
• Investigators: Principal Investigator: Marina Baretti, MD, SKCCC Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: August 19, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Carcinoma; Immunotherapy; Biliary Tract Cancer; Tremelimumab; Anti PD-L1; Hiltonol; Duvalumab; mBTCvax (peptide vaccine + Poly-ICLC (Hiltonol)); Anti-Cytotoxic T-lymphocyte antigen 4 (CTLA-4)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Neoplasms, Glandular and Epithelial; Biliary Tract Neoplasms; Carcinoma; Diabetes Mellitus, Insulin-Dependent, 12; Amino Acids, Peptides, and Proteins; durvalumab; tremelimumab; poly ICLC; Peptides
• Other Study ID Numbers: J2477; IRB00416341 (Other Identifier: Johns Hopkins Medical Institution)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No