TAEK-VAC-HerBy Vaccine for Brachyury and HER2 Expressing Cancer

Study Overview
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Brief Summary
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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 and gastric/gastroesophageal junction cancer patients for combination treatment of TAEK-VAC-HerBy vaccine and therapeutic HER2 antibodies (trastuzumab, pertuzumab). Patients in both stages will receive TAEK-VAC-HerBy intravenously, every three weeks, three administrations in total.

Official Title
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Phase 1 Trial of Intravenous Administration of TAEK-VAC-HerBy Vaccine Alone and in Combination With HER2 Antibodies in Patients With Advanced Cancer.

Conditions
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Chordoma, HER2-positive Breast Cancer, HER2-positive Gastric/Gastroesophageal Junction Cancer

Intervention / Treatment
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* Biological: TAEK-VAC-HerBy


Participation Criteria
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Eligibility Criteria
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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. Patients are required to be on active treatment with HER2 antibodies (trastuzumab, pertuzumab) prior to and during study treatment. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E7 Inf.U)<br>TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10E7 Inf.U. | Biological: TAEK-VAC-HerBy<br>* TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose defined in stage 1. During stage 2, it may also be administered concurrently with a HER2 antibody(ies) (trastuzumab, pertuzumab).<br>|
| Experimental: Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E8 Inf.U)<br>TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10E8 Inf.U. | Biological: TAEK-VAC-HerBy<br>* TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose defined in stage 1. During stage 2, it may also be administered concurrently with a HER2 antibody(ies) (trastuzumab, pertuzumab).<br>|
| Experimental: Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E9 Inf.U)<br>TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10E9 Inf.U. | Biological: TAEK-VAC-HerBy<br>* TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose defined in stage 1. During stage 2, it may also be administered concurrently with a HER2 antibody(ies) (trastuzumab, pertuzumab).<br>|
| Experimental: Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E10 Inf.U)<br>TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10E10 Inf.U. | Biological: TAEK-VAC-HerBy<br>* TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose defined in stage 1. During stage 2, it may also be administered concurrently with a HER2 antibody(ies) (trastuzumab, pertuzumab).<br>|
| Experimental: Stage 2: Chordoma Cancer Cohort<br>TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level defined in stage 1. | Biological: TAEK-VAC-HerBy<br>* TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose defined in stage 1. During stage 2, it may also be administered concurrently with a HER2 antibody(ies) (trastuzumab, pertuzumab).<br>|
| Experimental: Stage 2: HER2-positive Breast Cancer Cohort (Trastuzumab + TAEK-VAC-HerBy)<br>TAEK-VAC-HerBy will be administered intravenously to patients who are on stable dose of trastuzumab, every three weeks with three administrations in total at the dose defined in stage 1. | Biological: TAEK-VAC-HerBy<br>* TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose defined in stage 1. During stage 2, it may also be administered concurrently with a HER2 antibody(ies) (trastuzumab, pertuzumab).<br>|
| Experimental: Stage 2: HER2-positive Breast Cancer Cohort (Trastuzumab + Pertuzumab + TAEK-VAC-HerBy)<br>TAEK-VAC-HerBy will be administered intravenously to patients who are on stable dose of trastuzumab and pertuzumab. TAEK-VAC-HerBy will be administered every three weeks with three administrations in total at the dose defined in stage 1. | Biological: TAEK-VAC-HerBy<br>* TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose defined in stage 1. During stage 2, it may also be administered concurrently with a HER2 antibody(ies) (trastuzumab, pertuzumab).<br>|
| Experimental: Stage 2: HER2-positive Gastric/GEJ cancer cohort (Trastuzumab + TAEK-VAC-HerBy)<br>TAEK-VAC-HerBy will be administered intravenously to HER2-positive gastric/GEJ cancer patients who are on stable dose of trastuzumab. TAEK-VAC-HerBy will be administered every three weeks with | Biological: TAEK-VAC-HerBy<br>* TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose defined in stage 1. During stage 2, it may also be administered concurrently with a HER2 antibody(ies) (trastuzumab, pertuzumab).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients with Dose Limiting Toxicity (DLT) | Frequency of patients with DLTs | DLT evaluation period is 30 days after the last vaccine dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brachyury, HER2-expessing cancer