Inclusion Criteria: 

• Diagnosis: Patients must have histologically confirmed chordoma by the pathology department of the site to enroll the patient on trial, which is metastatic or unresectable locally advanced. Patients with potentially curable disease are eligible if the patient refuses therapy with curative intent and all other eligibility criteria are met.
• Patients must have measurable disease by RECIST 1.1.
• Patient must be scheduled to have radiation therapy to at least 1 target lesion with a minimum biologic equivalence of 8Gy in 1 fraction (see Section 6.3.1.1 for equivalent doses). Any lesion irradiated within the previous 1 year cannot be a RECIST 1.1 target lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at trial entry.
• Age ≥ 12 years old.
• Patients must have normal organ and marrow function as defined below:
  • Serum creatinine ≤ 1.5 x upper limit of normal OR creatinine clearance on a 24-h urine collection of ≥ 60 mL/min;
  • Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 x the upper limits of normal;
  • Total bilirubin ≤ 1.5 x upper limit of normal OR in patients with Gilbert’s syndrome, a total bilirubin ≤ 3.0 x upper limit of normal;
  • Hematological eligibility parameters (within16 days of initiating treatment):
    • Granulocyte count ≥ 1,500/mm3;
    • Platelet count ≥ 100,000/mm3;
    • Resting Pulse oximetry > 90% on room air.
• Must have recovered completely (Grade 1, stable, baseline) from any reversible toxicity associated with recent therapy. Typically this is 3–4 weeks for patients who most recently received cytotoxic therapy, except for the nitrosoureas and mitomycin C for which 6 weeks is needed for recovery.
• There should be a minimum of 2 weeks from any chemotherapy, small molecule/targeted therapy, immunotherapy and/or radiation prior to start of trial treatment.
• Females of child-bearing potential (FOCBP) and male partners of FOCBP must agree to use effective birth control or abstinence from screening to after the last vaccination therapy.
• Ability to understand and the willingness to sign a written informed consent or, in the case of ages 12 to 17, an assent document.

Exclusion Criteria:

• Concurrent systemic treatment for cancer.
• Patients with rapidly progressing disease at multiple sites.
• Patients with poorly differentiated or dedifferentiated chordomas.
• Chronic hepatitis B or C infection, because potential immune impairment caused by these disorders may diminish the effectiveness of this immunologic therapy.
• Any significant disease that, in the opinion of the investigator, may impair the patient’s tolerance of trial treatment.
• Significant dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity. However, patients with vitiligo or clinically stable autoimmune endocrine disease (i.e: Hashimoto’s thyroiditis) who are on appropriate replacement therapy (if such therapy is indicated) are eligible.
• Concurrent use of systemic steroids, except for physiologic doses of systemic steroid replacement or local (topical, ophthalmic, nasal, or inhaled) steroid use. Limited pharmacologic doses of systemic steroids (e.g., in patients with exacerbations of reactive airway disease or to prevent intravenous (IV) contrast allergic reaction or anaphylaxis in patients who have known contrast allergies) are allowed.
• Patients who are receiving any other investigational agents within 28 days before start of trial treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MVA-BN/FPV-Brachyury or other agents used in trial. History of allergic reaction to aminoglycoside antibiotics or egg products.
• Serious or uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with trial requirements.
• Pregnant women are excluded from this trial due to the unknown effects of the BN-Brachyury on the fetus or infant. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BN-Brachyury, breastfeeding should be discontinued if the mother is treated with BN-Brachyury. These potential risks may also apply to other agents used in this trial.
• Human immunodeficiency virus (HIV)-positive patients are ineligible because of the potential for decreased immune response to the vaccine.
• Significant cardiovascular disease, which includes but is not limited to New York Heart Association Heart Failure Class II or greater, myocardial infarction within the previous 3 months, unstable arrhythmias, unstable angina.
  • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% on a stable medical regimen that was optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate, are eligible.