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

NCT06564623 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J2477IRB00416341
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biliary Tract Cancers

Keywords

Biliary Tract Cancer; Duvalumab; Tremelimumab; Immunotherapy; mBTCvax (peptide vaccine + Poly-ICLC (Hiltonol)); Anti PD-L1; Anti-Cytotoxic T-lymphocyte antigen 4 (CTLA-4); Hiltonol; Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Progression Free Survival (PFS)

  4 years

• Overall Survival (OS)

  4 years

Study Arms (1)

Arm A - mBTCvax, Durvalumab and Tremelimumab

EXPERIMENTAL

Drug: mBTC vax [0.3 - 2.4 mg peptide + 0.5 mg Poly-ICLC (Hiltonol)]; Drug: Durvalumab; Drug: Tremelimumab

Interventions

mBTC vax [0.3 - 2.4 mg peptide + 0.5 mg Poly-ICLC (Hiltonol)] DRUG

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.

Also known as: Peptide + Poly-ICLC (Hiltonol)

Arm A - mBTCvax, Durvalumab and Tremelimumab

Durvalumab DRUG

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.

Also known as: IMFINZI®

Arm A - mBTCvax, Durvalumab and Tremelimumab

Tremelimumab DRUG

Patients will receive treatment on C1D1. Tremelimumab (300 mg) will be administered IV as a single dose on Day 1 of Cycle 1.

Also known as: IMJUDO®

Arm A - mBTCvax, Durvalumab and Tremelimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Private Philanthropic Funds: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

SKCCC Johns Hopkins Medical Institution

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms; Diabetes Mellitus, Insulin-Dependent, 12; Carcinoma

Interventions

Peptides; poly ICLC; durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins

Study Officials

• Marina Baretti, MD

  SKCCC Johns Hopkins Medical Institution

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostol, RN

CONTACT

410-614-3644; GIClinicalTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: August 21, 2024
• Study Start: May 27, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)