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

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

NCT ID: NCT06564623

Condition: Pancreatic Cancer

Conditions: Official terms:
Biliary Tract Neoplasms
Poly I-C
Durvalumab
Tremelimumab
Carboxymethylcellulose Sodium
Poly ICLC

Conditions: 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

Study type: Interventional

Study phase: Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: mBTC vax [0.3 - 2.4 mg peptide + 0.5 mg Poly-ICLC (Hiltonol)]
Description: 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.
Arm group label: Arm A - mBTCvax, Durvalumab and Tremelimumab

Other name: Peptide + Poly-ICLC (Hiltonol)

Intervention type: Drug
Intervention name: Durvalumab
Description: 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.
Arm group label: Arm A - mBTCvax, Durvalumab and Tremelimumab

Other name: IMFINZI®

Intervention type: Drug
Intervention name: Tremelimumab
Description: Patients will receive treatment on C1D1. Tremelimumab (300 mg) will be administered IV as a single dose on Day 1 of Cycle 1.
Arm group label: Arm A - mBTCvax, Durvalumab and Tremelimumab

Other name: IMJUDO®

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.

Criteria for 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. 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: SKCCC Johns Hopkins Medical Institution

Address:
City: Baltimore
Zip: 21231
Country: United States

Start date: November 2024

Completion date: November 2028

Lead sponsor:
Agency: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency class: Other

Collaborator:
Agency: AstraZeneca
Agency class: Industry

Collaborator:
Agency: Private Philanthropic Funds
Agency class: Other

Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06564623