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
1. Men and women > 18 years old.
2. Patients must be able to understand and be willing to sign a written informed consent
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,
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
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.
1. Receipt of an investigational agent within 28 days of the first planned dose of TVH
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
- 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
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
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.