taek-vac-herby vaccine for brachyury and her2 expressing cancer

Conditions: Chordoma; HER2-positive Breast Cancer

Summary: 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.


Eligibility criteria:
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.

Keywords: brachyury her2-expessing cancer