Interim results from a Phase I/II clinical trial using patients’ own T cells that have been genetically altered to attack multiple myeloma (MM) cells have been released. The study Chair presented these updated results today at the annual meeting of the American Society of Hematology (ASH).
The clinical trial was designed as a single arm open label study where patients are given standard of care (autologous stem cell transplant). This is followed by infusion of a patient’s own T cells that have been genetically engineered to carry receptors that help the T cells recognize and attack tumors, while sparing healthy tissue.
The objectives for the study are to evaluate 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). The target CT antigens in the study are NY-ESO-1 and LAGE-1. Anti-tumor responses are reported as best response by day 100 following the transplant and T cell infusion.
The initial six patient phase was completed in 2012 and based on encouraging preliminary results announced at ASH last December, the study was extended to a target enrollment of 26 patients. To date, 21 patients have been enrolled. 20 patients have received engineered T cells and have been assessed at day 100 for tumor responses to the treatment. 19 patients have reached a minimum of six month follow-up and 15 patients have reached one year follow-up.
After one year, patients are followed for disease status quarterly, and progression free and overall survival will be collected as the study follow-up matures. Patients are also monitored no less than bi-annually for safety and correlatives specific to the engineered T cells.
Multiple myeloma is a hematologic cancer localized to the bone marrow and is currently incurable in most patients. With standard therapy, long-term response rates are low and the median survival for patients with this disease is three to five years.
The clinical study focuses on this unmet medical need and includes patients who have received prior treatment for their myeloma or who have disease considered to be high risk, who are eligible for an autologous stem cell transplant (auto-SCT), and whose tumor expresses NY-ESO and/or LAGE-1. Auto-SCT 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 gene modified T cells occurs two days following auto SCT. 2
Dr. Aaron Rapoport, the Chair of the clinical study, presented abstract 766 entitled “Engineered T-Cells Expressing An HLA-Restricted Affinity-Enhanced TCR in Advanced Multiple Myeloma Patients Post Auto-SCT Engraft and Are Associated with Encouraging Post Auto-SCT Responses”.
He reports that infusions of engineered T cells have been well tolerated. The overall best response rate at 100 days is 77%. This rate is encouraging in these patients, of whom approximately 50% have high risk disease, 25% have received prior transplant, and NY-ESO expression is associated with poor prognosis.
Of the 20 patients treated to date, 13 have ongoing responses, and seven have progressed. In cases of disease progression, a concomitant loss or reduction of engineered T cells, or a loss of antigen positivity on recurring tumor has been observed. Consequently, the protocol has been modified to allow for additional infusions without concomitant transplant, provided the patient’s tumor continues to express target antigen.
“The clinical responses seen in our patients are encouraging and are generally better than I expected from transplant alone,” says Dr. Rapoport, the Gary Jobson Professor in Medical Oncology at the University of Maryland School of Medicine and Associate Director of the Blood and Marrow Transplant Program at the University of Maryland Marlene and Stewart Greenebaum Cancer Center. “I look forward to making this technology available to patients outside of the transplant setting.”
Enrollment is nearly completed and a final study analysis in planned to start in late 2014. Interim safety and response data presented at the ASH conference is under preparation for publication in the first half of next year.
“This study has provided us with important insights into the activity of NY-ESO T cells,” said Mr. James Noble, Chief Executive Officer of Adaptimmune. “It has been a privilege to work with this translational team and we are encouraged by progress to date on this study and our studies in solid tumor indications.”
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.
The study was originally developed by Dr. Carl H. June at the University of Pennsylvania (UPenn) Abramson Cancer Center and Dr. Rapoport. Dr. Rapoport is the lead clinical investigator at the University of Maryland and protocol Chair. Dr. Edward Stadtmauer is the lead clinical investigator at the UPenn Abramson Cancer Center, and Dr. Dan Vogl is a sub-investigator at UPenn. Dr. Michael Kalos led correlative studies at UPenn during his tenure as Director of the Translational and Correlative Sciences Laboratory (TCSL) at UPenn (now at Eli Lilly), and Dr. Simon Lacy is completing these studies at the TCSL on his behalf. Initially, Dr. June served as the regulatory sponsor (FDA representative) for the study and T cell manufacturing was performed at the Clinical Cell and Vaccine Production Facility at the University of Pennsylvania directed by Dr. Bruce Levine. In April 2013, following the Novartis engagement of UPenn for CD19 engineered T cell therapy in CLL and ALL, Adaptimmune assumed the sponsorship and T cell manufacturing roles for this study. Adaptimmune is also the financial sponsor for the study and owns the T cell receptor technology. 3
Adaptimmune has also opened a new 10 patient pilot study, designed to evaluate the safety and anti-tumor effects of the engineered T cells without transplant. This trial is now enrolling at the University of Maryland in Baltimore, Maryland, and the City of Hope in Duarte, California.
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 NCT01892293.
Other trials in ovarian cancer, melanoma and synovial sarcoma are ongoing in the U.S. and can be found on clincialtrials.gov.