Clinical trial NCT04246671: TAEK-VAC-HerBy Vaccine for Brachyury and HER2 Expressing Cancer
Official title: Phase 1 Trial of Intravenous Administration of TAEK-VAC-HerBy Vaccine Alone and in Combination With HER2 Antibodies in Patients With Advanced Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chordoma
HER2-positive Breast Cancer
Keywords: Brachyury
HER2-expessing cancer
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
First posted: 2020-01-29
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Patients with Dose Limiting Toxicity (DLT)
timeFrame: DLT evaluation period is 30 days after the last vaccine dose
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Phoenix
state: Arizona
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Augusta
country: United States
facility: Georgia Cancer Center Augusta University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington Medicine Seattle
name: Mary (Nora) L Disis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wedekind MF, Widemann BC, Cote G. Chordoma: Current status, problems, and future directions. Curr Probl Cancer. 2021 Aug;45(4):100771. doi: 10.1016/j.currproblcancer.2021.100771. Epub 2021 Jul 1.