targeting driver oncogenes with a peptide vaccine plus durvalumab and tremelimumab for patients with biliary tract cancers (btc)

Conditions: Biliary Tract Cancers

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.


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.

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