Date: 2016-06-04
Type of information: Presentation of results at a congress
phase: 1b
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Advantagene (USA - MA)
Product: aglatimagene besadenovec (AdV-tk) followed by valacyclovir
Action
mechanism: immunotherapy product/gene therapy. The product is based on Gene Mediated Cytotoxic Immunotherapy™ (GMCI). Upon administration, GMCI will generate a precise and robust patient specific immune response, attacking a patient’s solid tumors, distant metastases, or minimum residual disease. The technology consists of a series of small gauge, relatively painless injections at the tumor site or target tissue followed by the oral administration of an activating prodrug. The initial injections deliver aglatimagene besadenovec (AdV-tk), a gene vector derived from an adenovirus and engineered to deliver the thymidine kinase (tk) gene, derived from the Herpes Simplex virus, to the target cells. The target tissues and cells then produce the TK protein. Cells that multiply in the neighborhood of where the TK protein was delivered and is now expressed then become susceptible to the toxic effects of valacyclivir. Administration of valacyclivir then causes a cytotoxic biochemical reaction at the site of administration that leads to the death of multiplying tumor cells, cells repairing themselves from radiation or chemotherapy damage, and endothelial cells from growing tumor vessels. A subsequent cascade of immuno-stimulatory events, including the production and recruitment of disease fighting cytokines and cancer killing T-Cells, amplified by TK’s “super-antigen” characteristics, stimulates the in situ development of a precise, patient-specific anti-tumor immune effect to combat cancer cells. As a result, massive amounts of newly created T-cells, primary weapons used by the body to fight cancer, now recognize cells expressing a patient’s unique TAAs. These T-cells will identify, attack and destroy cancer cells expressing these antigens both at the site of the tumor and anywhere else in the body. Some of these new T-cells, called memory T-cells, can remain for years, patrolling the body for remaining cancer cells and providing a durable “vaccine like” effect, resulting in the eradication of tumors in some cases or slowing their growth or spread in others.
Disease: malignant pleural effusion
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This is a phase I study of intrapleural AdV-tk therapy in patients with malignant pleural effusion (MPE). The primary objective is to test the safety of intrapleural AdV-tk therapy. Secondary objectives are to evaluate clinical efficacy and biologic activity. (NCT01997190)
Latest
news: * On June 4, 2016, Advantagene announced the presentation of safety and interim efficacy data from a Phase 1b clinical trial of its novel Gene Mediated Cytotoxic Immunotherapy (GMCI®) in combination with standard of care chemotherapy in patients with malignant pleural effusion (MPE). The study is being conducted in collaboration with the University of Pennsylvania. The primary end-point of this dose escalation trial was to evaluate the safety of GMCI® using intra-pleural delivery of aglatimagene besadenovec to stimulate an anti-tumor immune response followed by standard chemotherapy. Eligible patients had malignant pleural effusion requiring a pleural catheter. Nineteen patients were enrolled and completed therapy, 3 in each of 3 cohorts followed by an additional 10 patient expansion of the third cohort. Patients in cohort 2 (high vector dose group) experienced symptoms related to immune stimulation, including transient cytokine release syndrome (CRS), with fever, nausea and chills (grade 2) plus hypotension in one patient. In cohort 3, the addition of celecoxib effectively controlled the CRS symptoms. The study included fourteen malignant mesothelioma patients, all with poor prognostic factors including sarcomatoid histology, multiply relapsed or not surgical candidates due to comorbidities. The study also enrolled four stage 4 non-small cell lung cancer (NSCLC) patients and one stage 4 breast cancer patient. In the high dose group, disease control rate was 79% with partial response by RECIST criteria in five patients (36% PR rate), three with mesothelioma and two NSCLC. Median overall survival was 13.6 months for the high dose group. Seven patients are still alive and continue in active follow up (5-21months), including three NSCLC patients with progression free survival of 6.8-12.9 months and overall survival at 12.9- 17.4 months. These results have been presented by Dr. Charu Aggarwal, MD, MPH, Assistant Professor in Hematology-Oncology at University of Pennsylvania in a poster presentation (abstract # 3081) at the 2016 American Society of Clinical Oncology (ASCO) meeting held in Chicago.
