Adaptimmune announced that it has opened a Phase I/II, dual site, two-cohort, open-label clinical trial in multiple myeloma at the University of Maryland and the University of Pennsylvania testing its enhanced T cell receptor T cell therapy.
Adaptimmune is focused on the use of T cell therapy to treat cancer, with the body’s own machinery - the T lymphocyte cell - being used to target and destroy cancerous cells. This trial is designed to investigate the safety, bioactivity and anti-tumor effect of infusion of patients’ own T cells that have been genetically modified to express a high affinity T cell receptor (TCR) specific for a type of tumor antigen (protein) known as a cancer testis antigen (CT antigen).
During the trial, TCRs that have been developed using Adaptimmune’s unique TCR enhancement technology will be deployed to target two CT antigens called Mage-A3/6 and NYESO-1. T cell manufacturing will be performed at the Clinical Cell and Vaccine Production Facility at the Perelman School of Medicine at the University of Pennsylvania.
Dr. Carl H. June at the Abramson Cancer Center of the University of Pennsylvania and Dr. Aaron Rapoport of the University of Maryland Greenebaum Cancer Center developed the study design, which was presented to the National Institutes of Health Recombinant DNA Advisory Committee last year. Dr. June is the regulatory sponsor (FDA representative) for the study, and Dr. Edward Stadtmauer is the lead clinical investigator at the Abramson Cancer Center. Dr. Rapoport is the lead clinical investigator at the University of Maryland. Adaptimmune Ltd is the financial sponsor and owns the core T cell receptor technology.
Multiple myeloma is a hematologic cancer localized to the bone marrow. With standard therapy, long- term response rates are low, and the median survival for patients with this disease is 3-5 years. The clinical trial focuses on this unmet medical need and will include patients who have received prior treatment for their myeloma and who are eligible for an autologous stem cell transplant (ASCT). ASCT is the transplant of a patient’s own stem cells, which is a standard of care for treatment of multiple myeloma in the U.S. Infusion of the CT antigen-specific T cells will occur just following ASCT. Drs. Rapoport, Stadtmauer and June have collaborated and extensively published on three prior clinical trials evaluating T cell infusion post ASCT, and have demonstrated that the procedure is safe and promotes reconstitution of the immune system. The aim of the current trial is to improve the anti-tumor efficacy of the T cell infusion by genetically redirecting the T cells to specifically recognize the patients’ tumor.
“This trial combines a series of technological advances in vector design, T-cell manufacturing, and TCR engineering,” says Dr. June. “The data emerging from this study in the next twelve months could significantly advance the field of gene-based T-cell therapeutics.”
“I am very enthusiastic about this study,” says Dr. Rapoport. “"The combination of autologous stem cell transplantation and immune reconstitution with tumor-specific T cells has the potential to have a powerful therapeutic effect."
A total of 12 patients will be enrolled in the trial over a period of two years, with six patients participating in each of the NYESO-1 and MAGE-A3/6 cohorts in accordance with a genetic randomization scheme based on a patient’s immune system (HLA-A) and tumor antigen status.
We are enormously pleased to be working with the world leaders in T-cell immunotherapy for multiple myeloma,” says James Noble, CEO of Adaptimmune. “Myeloma is an important clinical indication with which to evaluate our CT antigen specific TCRs because T cell immunotherapy fits so well with routine stem cell transplantation, and the effects of the T cells can be rapidly assessed.”
Additional study details and contact information for patients interested in finding out more about participation can be found at clincialtrials.gov, under trial identifier number NCT01352286.