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

NCT ID: NCT06564623

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-27
• Study Completion Date: 2029-05-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - mBTCvax, Durvalumab and Tremelimumab

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Durvalumab

Intervention Type: 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.

Tremelimumab

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Peptide + Poly-ICLC (Hiltonol); IMFINZI®; IMJUDO®

Eligibility Criteria

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.

• 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Private Philanthropic Funds

OTHER

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marina Baretti, MD

Role: PRINCIPAL_INVESTIGATOR

SKCCC Johns Hopkins Medical Institution

Locations

SKCCC Johns Hopkins Medical Institution

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Colleen Apostol, RN

Role: CONTACT

GIClinicalTrials@jhmi.edu

410-614-3644

Facility Contacts

Colleen Apostol, RN

Role: primary

GIClinicalTrials@jhmi.edu

410-614-3644

Other Identifiers

IRB00416341

Identifier Type: OTHER

Identifier Source: secondary_id

J2477

Identifier Type: -

Identifier Source: org_study_id