A Phase 1 open label trial of intravenous administration of TAEK-VAC-HerBy vaccine in patients with advanced brachyury and/or HER2- expressing cancer. The study will be completed in 2 stages. In Stage 1 patients will be enrolled and treated according to a 3+3 dose escalation scheme. Up to 4 dose levels will be explored to determine the recommended dose of TAEK-VAC-HerBy for Stage 2 of the trial. Stage 2 will enroll either chordoma patients for treatment with TAEK-VAC-HerBy alone, or HER2- positive breast cancer patients for combination treatment of TAEK-VAC-HerBy vaccine and therapeutic HER2 antibodies (trastuzumab). Patients in both stages will receive TAEK-VAC-HerBy intravenously, every three weeks, three administrations in total.

Inclusion Criteria:

General inclusion criteria, apply to all cohorts:

• Men and women ≥18 years old.
• Patients must have histologically documented malignant tumor which is unresectable locally advanced or metastatic.
• ECOG performance status 0 or 1
• Patients must have normal organ and bone marrow function as defined in the protocol.
• Normal left ventricular ejection fraction (LVEF) ≥50%.
• Troponin I within normal limits.
• A maximum cumulative dose of prior doxorubicin ≤360 mg/m2 or epirubicin ≤720 mg/m2
• Any approved cancer therapy (except HER2 antibodies) must be completed at least 3 weeks or 5 half-lives for small molecule inhibitors, whichever is shorter, prior to the first planned dose of TVH vaccine.
• HER-2 positive cancer: Patients are required to be on active treatment with HER2 antibodies (trastuzumab) prior to and during study treatment.
• Chordoma patients with progressive extracranial chordoma (base of skull is permitted) not amenable for surgical resection with curative intent, nor for radiation therapy will be enrolled.
• Patients must have recovered (Grade 1 or baseline) from any clinically significant toxicity associated with prior therapy.
• Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1.

Exclusion Criteria:

• Known metastatic disease to the central nervous system, unless previously treated and responded with a minimum stable disease over 2 CT scans separated at least 4 weeks from each other, and more than 6 weeks since the last dose of dexamethasone.
• History of allergy or untoward reaction to prior vaccination with vaccinia virus, aminoglycoside antibiotics, ciprofloxacin, or egg products.
• Subjects should have no known evidence of being immunocompromised.
• Chronic administration (defined as >5 consecutive days of >15 mg of prednisone (or equivalent) per day) of systemic corticosteroids within 14 days of the first planned dose of TAEK-VAC-HerBy vaccine. Use of inhaled steroids, nasal sprays, eye drops, and topical creams is allowed. Steroids premedication for CT scans is allowed.
• Clinically significant cardiomyopathy, coronary disease, congestive heart failure (NYHA class III or IV) or reduced as per institutional standards LVEF, poorly controlled hypertension (systolic >180 mm Hg or diastolic >100 mm Hg) or cerebrovascular accident within 1 year.
• Known history of, or any evidence of active, non-infectious pneumonitis or primary pulmonary fibrosis.