Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04246671
Recruitment Status : Recruiting
First Posted : January 29, 2020
Last Update Posted : February 21, 2022
Sponsor:
Information provided by (Responsible Party):
Bavarian Nordic

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 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.

Condition or disease Intervention/treatment Phase
Chordoma Breast Cancer Gastric/Gastroesophageal Junction Cancer Ovarian Cancer Prostate Cancer Colorectal Cancer Pancreatic Cancer Hepatocellular Cancer Merkel Cell Cancer Small Cell Lung Cancer Biological: TAEK-VAC-HerBy Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : August 10, 2020
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2026


Arm Intervention/treatment
Experimental: Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E7 Inf.U)
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
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).

Experimental: Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E8 Inf.U)
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
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).

Experimental: Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E9 Inf.U)
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
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).

Experimental: Stage 1 dose escalation: TAEK-VAC-HerBy (1x10E10 Inf.U)
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
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).

Experimental: Stage 2: Chordoma Cancer Cohort
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
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).

Experimental: Stage 2: HER2-positive Breast Cancer Cohort (Trastuzumab + 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.
Biological: TAEK-VAC-HerBy
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).

Experimental: Stage 2: HER2-positive Breast Cancer Cohort (Trastuzumab + Pertuzumab + TAEK-VAC-HerBy)
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
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).

Experimental: Stage 2: HER2-positive Gastric/GEJ cancer cohort (Trastuzumab + TAEK-VAC-HerBy)
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
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).




Primary Outcome Measures :
  1. Patients with Dose Limiting Toxicity (DLT) [ Time Frame: DLT evaluation period is 30 days after the last vaccine dose ]
    Frequency of patients with DLTs



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

General inclusion criteria, apply to all cohorts:

  • Men and women >18 years old.
  • Patients must have a metastatic or recurrent locally advanced malignant tumor.
  • ECOG performance status 0 or 1
  • Patients must have normal organ and bone marrow function as defined below:

    • Serum creatinine ≤1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥40 mL/min.
    • Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3 x the ULN.
    • Total bilirubin ≤1.5 x ULN (in subjects with Gilbert's syndrome a total bilirubin ≤3.0 x ULN).
    • Hemoglobin >9 g/dL.
    • Platelet count ≥100,000/µL.
    • Absolute neutrophil count (ANC) ≥1000/µL.
  • 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 prior chemotherapy, targeted therapy, immunotherapy and/or radiation must be completed at least 4 weeks prior to the first planned dose of TVH vaccine
  • Patients must have recovered (Grade 1 or baseline) from any clinically significant toxicity associated with prior therapy.

Additional inclusion criteria for Stage 1

  • Patient population:

    • Patients with metastatic cancer with a high probability of brachyury expression (such as chordoma, breast, ovarian, prostate, colorectal, pancreatic, hepatocellular, Merkel cell, small cell lung cancer etc) and have progressed on at least two lines of systemic therapy.
    • Patients with unresectable locally advanced and metastatic breast and gastric/gastroesophageal junction cancer expressing HER2 at levels lower than the threshold required for definition of HER-2 positivity by ASCO/CAP (breast, gastric/GEJ, ovarian, bladder, salivary gland, endometrial, pancreatic and non-small-cell lung cancer, etc). Patients must have progressed on at least two lines of systemic therapy.
    • Patients with breast and gastric HER2- positive tumors as per ASCO/CAP must have progressed after receipt of:
  • Breast: at least 3 lines of HER2-targeting therapy
  • Gastric and gastroesophageal junction cancer: at the time of progression after 2 lines of HER2-targeting therapy.

    • Patients must have measurable or evaluable disease. Measurable disease is defined by RECIST 1.1.

Additional inclusion criteria for Stage 2

  • Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1.
  • Patient population:

    • Cohort 2: chordoma patients with extracranial lesions not amenable for surgical resection with curative intent, nor for radical radiation therapy. At least one target lesion not previously irradiated must be present, either metastatic or locoregional recurrence located outside of previously irradiated field.
    • Cohorts 3, 4, and 5: patients with HER2-positive tumors (breast, gastric/GEJ).
    • Cohort 4 will include patients on treatment with trastuzumab plus pertuzumab with less than CR (non-improving PR or SD) or as a window of opportunity at the first evidence of progression and before initiating the next line of standard treatment.
  • HER2 status must be determined as defined by the most recent ASCO/CAP guidelines for breast and gastric/gastroesophageal cancer.
  • For Cohorts 3, 4 and 5, patients must be on a stable dose of HER2 antibody(ies). Patient is defined to be on a stable dose of HER2 antibody(ies) if they have completed the chemotherapy component of regimens consisting on the combination of chemotherapy with HER2-targeting antibodies and have continued with the antibody for a minimum of 2 months.

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 as listed below:

    • Human immunodeficiency virus (HIV) positivity, chronic hepatitis infection, including B and C
    • Active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, and psoriasis not requiring systemic treatment are permitted
    • Immunosuppressive therapy, post-organ transplant
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04246671


Contacts
Layout table for location contacts
Contact: Tatiana Adams, MD, PhD +49 172 840 04 36 info@bavarian-nordic.com

Locations
Layout table for location information
United States, Arizona
Mayo Clinic - Phoenix, Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact       mayocliniccancerstudies@mayo.edu   
Principal Investigator: Mohamad Sonbol, MD         
United States, Florida
Mayo Clinic - Jacksonville, Florida Recruiting
Jacksonville, Florida, United States, 32224
Contact       mayocliniccancerstudies@mayo.edu   
Principal Investigator: Saranya Chumsri, MD         
H. Lee Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Aiana Cerezo, BS    813-745-6985    aiana.cerezo@moffitt.org   
Principal Investigator: Ricardo Costa, MD         
United States, Georgia
Georgia Cancer Center August University Recruiting
Augusta, Georgia, United States, 30912
Contact: Latasha McKie    706-721-4249    LGOMILLIONMCKIE@augusta.edu   
Principal Investigator: Priyanka Raval, MD         
United States, Minnesota
Mayo Clinic - Rochester, Minnesota Recruiting
Rochester, Minnesota, United States, 55905
Contact       mayocliniccancerstudies@mayo.edu   
Principal Investigator: Ciara O'Sullivan, MD         
United States, Oregon
Providence Cancer Institute Recruiting
Portland, Oregon, United States, 97213
Contact: Providence Cancer Institute    503-215-2614    CanClinRsrchStudies@providence.org   
Principal Investigator: David Page, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Kris Kauno    206-543-3829    kkauno@uw.edu   
Principal Investigator: Mary (Nora) Disis, MD         
Sponsors and Collaborators
Bavarian Nordic
Investigators
Layout table for investigator information
Principal Investigator: Mary (Nora) L Disis, MD University of Washington Medicine Seattle
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bavarian Nordic
ClinicalTrials.gov Identifier: NCT04246671    
Other Study ID Numbers: TAEK-VAC-HerBy-001
First Posted: January 29, 2020    Key Record Dates
Last Update Posted: February 21, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bavarian Nordic:
Brachyury
HER2-expessing cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Merkel Cell
Small Cell Lung Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Chordoma
Neoplasms by Site
Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Polyomavirus Infections
DNA Virus Infections
Virus Diseases
Infections
Tumor Virus Infections
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors