Overview

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

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.