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

Phase 1

Active, not recruiting

Brief 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E7 Inf.U)	TAEK-VAC-HerBy	TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10E7 Inf.U.
Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E8 Inf.U)	TAEK-VAC-HerBy	TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10E8 Inf.U.
Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E9 Inf.U)	TAEK-VAC-HerBy	TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10E9 Inf.U.
Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E10 Inf.U)	TAEK-VAC-HerBy	TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10E10 Inf.U.
Stage 2: Chordoma Cancer Cohort	TAEK-VAC-HerBy	TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level defined in stage 1.
Stage 2: HER2-positive Breast Cancer Cohort (Trastuzumab + TAEK-VAC-HerBy)	TAEK-VAC-HerBy	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.

Primary Outcome Measures

Name	Time	Method
Patients with Dose Limiting Toxicity (DLT)	DLT evaluation period is 30 days after the last vaccine dose	Frequency of patients with DLTs

Secondary Outcome Measures

Name	Time	Method

Locations (9): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Mayo Clinic - Phoenix
🇺🇸
Scottsdale, Arizona, United States
Providence Saint John's Health Center
🇺🇸
Santa Monica, California, United States
Georgia Cancer Center Augusta University
🇺🇸
Augusta, Georgia, United States
Mayo Clinic - Rochester
🇺🇸
Rochester, Minnesota, United States
Providence Cancer Institute
🇺🇸
Portland, Oregon, United States
University of Washington
🇺🇸
Seattle, Washington, United States
H. Lee Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Mayo Clinic - Jacksonville
🇺🇸
Jacksonville, Florida, United States