This study is a first in human Phase 1 study that involves patients with a type of cancer called HER2 (Human Epidermal Growth Factor Receptor 2) positive cancer. This study asks patients to volunteer to take part in a research study investigating the safety and efficacy of using special immune cells called HER2 chimeric antigen receptor specific cytotoxic T lymphocytes (HER2 specific CAR T cells), in combination with intra-tumor injection of CAdVEC, an oncolytic adenovirus that is designed to help the immune system including HER2 specific CAR T cell react to the tumor. The study is looking at combining these two treatments together, because we think that the combination of treatments will work better than each treatment alone. We also hope to learn the best dose level of the treatments and whether or not it is safe to use them together. In this study, CAdVEC will be injected into participants tumor at one tumor site which is most easiest to reach. Once it infects the cancer cells, activation of the immune response will occur so it can attack and kill cancer cells. (This approach may have limited effects on the other tumor sites that have not received the oncolytic virus injection, so, patients will also receive specific T cells following the intratumor CAdVEC injection.) These T cells are special infection-fighting blood cells that can kill cells infected with viruses and tumor cells. Investigators want to see if these cells can survive in the blood and affect the tumor. Both CAdVEC and HER2-specific autologous CAR T are investigational products. They are not approved by the FDA.
Treatment with CAdVEC:
On the first day of your treatment, participants will receive an injection of CAdVEC into
A blood sample will be obtained from the participant before the CAdVEC intratumor injection .
Depending on the location of the tumor, different techniques can be used for the injection
into your tumor. The most common route of injection is ultrasound-guided percutaneous (needle
puncture in the skin) injection, but endoscopic (using a lighted, flexible instrument called
an endoscope) ultrasound-guidance will be used for some patients as appropriate. Prior to
percutaneous injection, participants may receive an anti-anxiety medicine to calm them down,
to relieve muscle spasms, and provide sedation. If the participants tumor is injected during
an endoscopic procedure, the procedure may be done under sedation.
Treatment with HER2- specific autologous T Cells:
Earlier the participant gave blood for us to make HER2 targeting cytotoxic T-lymphocytes
(HER2- specific autologous T Cells). These cells are grown in the lab and frozen for
participants. Invesitgators made the cells by combining dendritic cells (DCs) or monocytes
with the T cells in the presence of produced mixtures of adenoviral proteins. Investigators
then put a new gene in to those T cells to make them specifically attract to and kill HER2
positive tumors. As the T cells grow, they are cultured by adding adenoviral proteins for
stimulation and expansion. Investigators call those T cells: HER2- targeting T cells (HER2-
specific autologous T Cells).
This study looks at different doses of HER2- specific autologous T Cells. The decision about
the dose participants receive is determined when enrolled on the study.
Seven dose levels will be evaluated. Cohorts of size 3 will be enrolled at each dose level
until 9 evaluable patients have been studied at a single dose. Each patient will receive an
intratumoral injection of CAdVEC alone or combined with an injection of HER2.CAR T cells.
CAdVEC intratumoral injection will be given as a single injection to a single appropriate
tumor site by direct, endoscopic, or image-guided injection on Day 1. The injection site will
be chosen based on a combination of criteria, including accessibility and safety of injection
site; tumor size; and anticipated tumor viability (e.g. avoid necrotic or cystic injection
sites). HER2.CAR T cells will be given intravenously on day 4 after CAdVEC injection, with a
3 day window (until day 7).
Before receiving the T cell infusion, participants may be given Benadryl (diphenhydramine)
and Tylenol (acetaminophen). Tylenol and Benadryl are given to prevent a possible allergic
reaction to the T cell administration.
Standard medical tests before treatment:
Before being treated, participants will receive a series of standard medical tests and
procedures as well as research blood draws.
Standard Medical tests during and after treatment:
During treatment, participants will receive standard medical tests and procedures as well as
research blood draws.
Study specific evaluations:
Investigators will follow participants closely after treatment for any side effects for at
least 2 years after the last infusion.
To learn more about the way the T cells are working in the body, an extra blood sample will
be taken before the CAdVEC injection, before the CAR T cell infusion, and at week 1, 2, 4 ,
6, months 3, 6, 9 and 12 after CAR T cell infusion. Thereafter every 6 months up to 5 years
and then yearly for 15 years. Investigators will use this blood to see how long the T cells
last and to look at the immune response to the cancer. Investigators may also ask to get a
tumor tissue biopsy at week 12 if necessary. Buccal swabs (cheek scraping) and urine will be
collected before CAdVEC injection, Days 2, 4 (or the day of CAR T-cell infusion), weeks 1 and
2 after CAR T cell infusion.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||December 2020||Phase 1||Interventional|
Primary Outcome 1 - Measure: Number of patients with dose limiting toxicity (DLT) by CTCAE 5.0
Primary Outcome 1 - Time Frame: 6 weeks after the HER2.CAR AdVST infusion or 6 weeks + 3 days after the CAdVEC injection.
This study will look at solid tumors (as a basket trial for any solid cancer) with HER2
positivity based on IHC
1. Histologically confirmed HER2 positive solid tumors, including but not limited to:
head and neck squamous cell carcinoma; cancer of the salivary glands; lung cancer;
breast cancer; bladder cancer; gastric cancer; esophageal cancer; colorectal cancer;
and pancreatic adenocarcinoma. HER2 positivity is defined as ≥2+ staining by IHC with
either the FDA-approved CB11 antibody (Leica) or anti HER2/neu (4B5) (VENTANA), which
refers to greater than weak-to-moderate staining intensity in >10% tumor cells.
2. The disease must be deemed by the appropriate multi-disciplinary tumor board
unsuitable for curative surgery, radiotherapy, systemic therapy, including checkpoint
inhibitors, or any combination of the above modalities.
3. Disease must have progressed after standard first line therapy, or without available
effective treatment options. Patients are still eligible if they have failed more than
one line of therapy.
4. The patient must have at least one tumor site appropriate for intratumoral injection.
5. The patient must have radiographically measurable disease as per RECIST 1.1.
6. The patient must have adequate organ function within 7 days prior to consent for
treatment as indicated by following measures:
- Hematologic: Absolute neutrophil count (ANC) ≥1.0 x 109/l; Hemoglobin ≥9 g/dl;
Platelet count ≥ 100 x 109/l; PT or PTT ≤ 1.5 x ULN unless the subject is
- Hepatic function: bilirubin < 2 x ULN, and AST and ALT < 3 x ULN
- Renal Function: serum creatinine <2 x the ULN or creatinine clearance >60 mL/min.
- Cardiac function: LVEF ≥ 55%.
7. Prior HER2 targeted therapy is allowed if delivered at least 4 weeks prior to the
8. Prior immunotherapy is allowed if it was delivered at least 4 weeks prior to the
9. Eastern Cooperative Oncology Group (ECOG) performance status 2 or less.
10. Females of childbearing potential must have a negative pregnancy test and agree to use
contraception during on-study protocol therapy.
11. Male subjects with pregnant partner/female partner of childbearing potential agree to
use barrier contraceptive during the study to minimize the risk of embryo-fetal
12. The patient is ≥ 18 years of age, and able to understand and give informed consent to
study related procedures and treatments.
1. Patients with any concurrent treatment that would compromise the study including but
not limited to continuous high dose corticosteroids (more than 10mg/day prednisone or
equivalent dose), lympho-depleting antibodies or cytotoxic agents, CNS metastasis
requiring continuous high-dose steroids (more than 10mg/day prednisone or equivalent
dose) or other active therapeutic intervention. This does not include stable,
previously-treated brain metastases.
2. Patients at significant risk of airway compromise or other critical obstruction (e.g.
bowel, ureter, etc.) in the event of possible post injection tumor inflammation based
on the investigative team's judgement.
3. History or evidence of active autoimmune disease requiring continuous systemic
corticosteroids, immunosuppressants or other disease modifying agents.
4. Evidence of significant immunosuppressive conditions, such as the following:
- Post organ transplant.
- Diagnosis of HIV or other immunodeficiency disorders.
5. Diagnosis of other malignancies within 5 years except for cutaneous basal cell or
squamous cell carcinoma, well-differentiated thyroid cancer, or localized prostate
6. Patients with known active infectious disease, such as hepatitis B or C infection.
7. Patient has had acute myocardial infarction within 6 months prior to enrollment for
8. Patients with abnormal left ventricular function (LVEF <55%). i .Injectable tumor site
is considered to incur a significant risk of major hemorrhage (e.g. located in the CNS
(brain), pulmonary parenchyma, and proximal to critical neurovascular structures).
j. Pregnant or breastfeeding females. k. Uncontrolled intercurrent illness including but
not limited to psychiatric illness and or social situations that in the opinion of the
investigator would compromise compliance of study requirements or put the patient at
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Daniel Wang, MD
Role: Principal Investigator
Affiliation: Baylor College of Medicine