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Intravenous TAEK-VAC-HerBy Vaccine Alone and in Combination Treatment in HER2 Cancer Patients

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ClinicalTrials.gov Identifier: NCT04246671
Recruitment Status : Recruiting
First Posted : January 29, 2020
Last Update Posted : October 1, 2021
Sponsor:
Information provided by (Responsible Party):
Bavarian Nordic

Tracking Information
First Submitted Date  ICMJE January 24, 2020
First Posted Date  ICMJE January 29, 2020
Last Update Posted Date October 1, 2021
Actual Study Start Date  ICMJE August 10, 2020
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 28, 2020)
Patients with Dose Limiting Toxicity (DLT) [ Time Frame: DLT evaluation period is 30 days after the last vaccine dose ]
Frequency of patients with DLTs
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravenous TAEK-VAC-HerBy Vaccine Alone and in Combination Treatment in HER2 Cancer Patients
Official Title  ICMJE Phase 1/2 Expansion Cohorts Trial of Intravenous Administration of TAEK-VAC-HerBy Vaccine Alone and in Combination With HER2- and PD-1/PD-L1 Antibodies in Patients With Advanced HER2-expressing Cancer
Brief Summary A Phase 1/2 open label trial of intravenous administration of TAEK-VAC-HerBy vaccine in patients with advanced HER2- expressing cancer. The study will be completed in 3 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. Stage 2 will enroll patients with HER2- positive breast and gastric cancer to administer the TAEK-VAC-HerBy vaccine in combination with HER2 antibodies. Stage 3 will enroll patients to evaluate the safety and tolerability of the TAEK-VAC-HerBy vaccine in combination with HER2 antibodies and PD-1/PD-L1 antibody. Patients, in all three stages, will receive TAEK-VAC-HerBy every three weeks, three administrations in total.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Gastric Cancer
  • Chordoma
  • Lung Cancer
  • Ovarian Cancer
  • Prostate Cancer
  • Colorectal Cancer
  • Pancreatic Cancer
  • Hepatocellular Cancer
  • Merkel Cell Carcinoma
  • Small-cell Lung Cancer
Intervention  ICMJE Biological: TAEK-VAC-HerBy
TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose indicated by the enrolled cohort. It may also be administered concurrently with a HER2 antibody or a checkpoint inhibitor depending on the trial stage.
Study Arms  ICMJE
  • Experimental: TAEK-VAC-HerBy Stage 1 (TVH 1x10^7 Inf.U)
    TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10^7 Inf.U.
    Intervention: Biological: TAEK-VAC-HerBy
  • Experimental: TAEK-VAC-HerBy Stage 1 (TVH 1x10^8 Inf.U)
    TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10^8 Inf.U.
    Intervention: Biological: TAEK-VAC-HerBy
  • Experimental: TAEK-VAC-HerBy Stage 1 (TVH 1x10^9 Inf.U)
    TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10^9 Inf.U.
    Intervention: Biological: TAEK-VAC-HerBy
  • Experimental: TAEK-VAC-HerBy Stage 1 (TVH 1x10^10 Inf.U)
    TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total at the dose level 1x10^10 Inf.U.
    Intervention: Biological: TAEK-VAC-HerBy
  • Experimental: TAEK-VAC-HerBy Stage 2 - (Trastuzumab + TVH)
    TAEK-VAC-HerBy will be administered to patients who are on stable dose of Trastuzumab. TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total.
    Intervention: Biological: TAEK-VAC-HerBy
  • Experimental: TAEK-VAC-HerBy Stage 2 - (T-DM1 + TVH)
    TAEK-VAC-HerBy will be administered to patients who are on stable dose of T-DM1. TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total.
    Intervention: Biological: TAEK-VAC-HerBy
  • Experimental: TAEK-VAC-HerBy Stage 2 - (Trastuzumab + Pertuzumab + TVH)
    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.
    Intervention: Biological: TAEK-VAC-HerBy
  • Experimental: TAEK-VAC-HerBy Stage 2 - (Her2 + TVH + PD1/PD-L1)
    TAEK-VAC-HerBy will be administered intravenously every three weeks with three administrations in total in combination with a HER2 antibody and a PD-1/PD-L1 Antibody.
    Intervention: Biological: TAEK-VAC-HerBy
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 28, 2020)
45
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Men and women > 18 years old.
  2. Patients must be able to understand and be willing to sign a written informed consent document.
  3. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
  4. Patients must have a metastatic or recurrent locally advanced malignant tumor, histologically documented.
  5. Patients must have completed or had disease progression on at least one prior line of disease-appropriate therapy for locally advanced or metastatic disease, or not be candidates for therapy of proven efficacy for their disease.
  6. ECOG performance status 0 or 1
  7. Patients must have normal organ and bone marrow function as defined below:

    • Renal function:

    Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dL] Male CrCl = [(140 - age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL] •Liver function: 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), or < 5 x ULN, if liver metastases are present.

    •Hematological parameters (within one week of starting therapy):

    •Hemoglobin > 9 g/dL.

    •Platelet count ≥ 100,000/µL.

    •Absolute neutrophil count (ANC) ≥ 1/µL.

  8. Normal left ventricular ejection fraction (LVEF) ≥50%.
  9. Troponin I within normal limits.
  10. A maximum cumulative dose of prior doxorubicin ≤ 360 mg/m2 or epirubicin ≤ 720 mg/m2
  11. 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, with the following exceptions, assuming any toxicity related to these therapies is well controlled or resolved and the patient has been on that therapy for at least 8 weeks at the time of enrollment:

    • Breast cancer - patients may remain on hormonal therapy if indicated (Estrogen Receptor/Progesterone Receptor positive [ER/PR+]).
  12. Patients must have recovered (Grade 1 or baseline) from any clinically significant toxicity associated with prior therapy.
  13. Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to administration of TVH vaccine or HER2-targeting antibodies. Both men and women must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) through the trial treatment period and for at least 3 months after the last vaccination therapy for TAEK-VAC-HerBy monotherapy (Stage 1) and 7 months for combination treatment arms (Stage 2 and 3).

    ADDITIONAL INCLUSION CRITERIA FOR STAGE 1 ONLY

  14. Patient population:

    •Patients with metastatic cancer with a high probability of brachyury expression (such as lung, breast, ovarian, prostate, colorectal, pancreatic, hepatocellular, Merkel cell, small cell lung cancer or chordoma; other tumors may be included as data on the level of brachyury in those tumors becomes available) 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.

    • Other unresectable locally advanced or metastatic cancers (such as ovarian, bladder, salivary gland, endometrial, pancreatic and non-small-cell lung cancer NSCLC, etc) with HER2 amplification by adjusted fold change detected by NGS, FISH detected HER2/CEP17 ≥2, or any level of HER2 detected by IHC are acceptable since no HER2 targeted therapy is FDA-approved for those indications. Patients that are enrolled with tumors having HER2 expression below the threshold required for definition of HER2 positivity by ASCO/CAP 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 all therapies known to confer clinical benefit: oBreast: trastuzumab, pertuzumab, T-DM1. These patients may have also received tyrosine kinase inhibitors (TKI) such as lapatinib or neratinib as well as different lines of chemotherapy. oGastric and gastroesophageal junction cancer: at the time of progression after trastuzumab in combination with chemotherapy as first line therapy.
  15. Patients must have measurable or evaluable disease. Measurable disease is defined by RECIST 1.1. In the case of evaluable disease, patients should have cancer-related symptoms to justify risk. Evaluable disease is defined as any of the following:

    • Elevated serum tumor marker known to be related to the patient's tumor burden.
    • Clear radiographic or physical exam evidence of tumor which does not meet RECIST 1.1 measurability criteria.

ADDITIONAL INCLUSION CRITERIA FOR STAGES 2 AND 3

14. Patients must have measurable disease by computed tomography (CT)/ magnetic resonance imaging (MRI) per RECIST 1.1

15. Patient population:

•Cohort 2 will include patients with HER2-positive tumors (breast, gastric).

  • Cohorts 3 and 4 will include only patients with metastatic HER2-positive breast cancer: oCohort 3 will include patients with less than CR to T-DM1 treatment (SD, PR) or patients at the first evidence of progression while on T-DM1 treatment and before initiating an alternative systemic treatment oCohort 4 will include patients on treatment with trastuzumab plus pertuzumab with less than CR (PR or SD) or as a window of opportunity at the first evidence of progression and before initiating the next line of standard treatment
  • Cohort 5 will include patients with treatment combination used for a cohort of Stage 2 which completed recruitment first (or a subgroup of 6 patients within the Cohort 2: 2a (breast) or 2b (gastric). The cohort needs to satisfy criteria listed above.

    16. HER2 status must be determined as defined by the most recent ASCO/CAP guidelines for breast and gastric/gastroesophageal cancer.

    17. For Cohort 2, 3 and 4, 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.

ADDITIONAL INCLUSION CRITERIA FOR STAGE 3

18. Availability of formalin fixed paraffin embedded (FFPE) tumor sample (consecutive 10 x 4µm sections, not older than 3 years) for PD-L1 expression determination. Result availability is not mandatory for patient inclusion into the trial.

19. Patients must be immune check-point inhibitor treatment naïve.

Exclusion Criteria:

  1. Receipt of an investigational agent within 28 days of the first planned dose of TVH vaccine.
  2. Concurrent chemotherapy or radiotherapy or other immunotherapy not explicitly allowed by inclusion criteria for that stage of the trial.
  3. During the Stage 2 and 3, patients with history of other malignancies within last 5 years with an estimated risk of recurrence higher than 50% are excluded. Examples of low risk of recurrence malignancies are non-melanoma skin cancer, in situ cervical, superficial bladder cancer, etc.
  4. 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.
  5. History of allergy or untoward reaction to prior vaccination with vaccinia virus, aminoglycoside antibiotics, ciprofloxacin, or egg products.
  6. Active infection within 72 hours prior to vaccination.
  7. Administration of antibiotics within 7 days prior to initial vaccination.
  8. 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
  9. 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.
  10. Vaccinations or planned vaccinations with a live vaccine within 30 days prior to the trial vaccination or with an inactivated vaccine within 14 days prior to the trial vaccination.
  11. Pregnant or breastfeeding women.
  12. 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.
  13. Known history of, or any evidence of active, non-infectious pneumonitis or primary pulmonary fibrosis.
  14. Any other condition, which in the opinion of the Investigator, would indicate the subject is a poor candidate for treatment with TVH vaccine or would interfere with the evaluation of the trial endpoints.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tatiana Adams, MD, PhD +49 172 840 04 36 info@bavarian-nordic.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04246671
Other Study ID Numbers  ICMJE TAEK-VAC-HerBy-001 Phase 1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bavarian Nordic
Study Sponsor  ICMJE Bavarian Nordic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mary (Nora) L Disis, MD University of Washington Medicine Seattle
PRS Account Bavarian Nordic
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP