Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors

Summary

Participation Requirements

Description

Treatment with CAdVEC: On the first day of your treatment, participants will receive an injection of CAdVEC into your tumor. 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 ...

Treatment with CAdVEC: On the first day of your treatment, participants will receive an injection of CAdVEC into your tumor. 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.

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