At a glance
ClinicalIndex Comparison Record- ✓Histologically confirmed advanced refractory HER2 positive solid tumor
- ✓HER2 positivity ≥2+ staining by IHC (CB11 or 4B5 antibody)
- ✓Disease unsuitable for curative treatments including surgery, radiotherapy, systemic therapy, or combination
- ✓Disease progressed after standard first line therapy or no available effective treatment options
- ✕Active autoimmune disease requiring continuous systemic corticosteroids >10mg/day prednisone or equivalent
- ✕Post organ transplant
- ✕HIV or other immunodeficiency disorders
- ✕Other malignancies within 5 years (except cutaneous basal/squamous cell carcinoma, well-differentiated thyroid cancer, localized prostate or cervical cancer)
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A First in Human Phase I Trial of Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR T Cells in Patients With Advanced HER2 Positive Solid Tumors
In Brief
A Phase 1 clinical trial evaluating CAdVEC for Bladder Cancer and 9 related conditions. Currently recruiting, targeting 45 participants across 1 site.
Detailed Summary
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.
Study Details
Timeline
Interventions
The intratumoral administration of CAdVEC will create a pro-inflammatory tumor microenvironment and will promote the recruitment and expansion of adoptively transferred HER2 specific CAR T cells via CAR (tumor antigen). We expect HER2 CAR T cells expanded at primary tumor sites will re-circulate and target metastasized tumors. The combination we propose to test has the potential to overcome each of the established individual limitations of oncolytic viruses and of CAR T-cells. Testing each element separately would not be beneficial or informative, since the combination therapy is anticipated to have unique profiles of both therapeutic benefit and potential toxicities.