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.
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.
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.
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
Single group
mBTC vax [0.3 - 2.4 mg peptide + 0.5 mg Poly-ICLC (Hiltonol)]
DrugPatients 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
DrugPatients 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
DrugPatients will receive treatment on C1D1. Tremelimumab (300 mg) will be administered IV as a single dose on Day 1 of Cycle 1.
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.
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.
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.
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.
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
AstraZeneca
Collaborator
Private Philanthropic Funds
Collaborator
