Clinical Trials

Date: 2013-12-10

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the annual meeting of the American Society of Hematology (ASH)

Company: Adaptimmune (UK)

Product: NY-ESO-1c259-T cell therapy product

Action mechanism: cell therapy.

Disease: multiple myeloma

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

• This Phase I/II study is a pilot, dual-cohort, two-site, clinical trial evaluating the safety and activity of redirected autologous T cells expressing a high affinity TCR specific for MAGE-A3/6 or NY-ESO-1 administered post ASCT in patients with advanced myeloma (NCT01352286). 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. The clinical study was designed as a single arm open label study where patients are given standard of care (autologous stem cell transplant) in conjunction with engineered T cells. The critical step in this new approach is that the infused T cells have been genetically engineered to carry receptors that help the T cells recognize and attack a tumor, while sparing healthy tissue.

 

Latest news:

• • On December 10, 2013, Adaptimmune has announced interim results from its Phase I/II clinical trial using patients’ own T cells that have been genetically altered to attack multiple myeloma cells. The results were announced at the American Society of Hematology (ASH) meeting.  An initial six patient phase of the trial was completed in 2012 and based on encouraging preliminary results announced at ASH last December (see below), 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. To date, 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 while 15 patients have reached one year follow-up. 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. 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 the overall best response rate at 100 days is 77% - an encouraging rate in these patients, of whom approximately 50% have high risk disease. Enrollment is now 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. • On December 10, 2012, Adaptimmune has announced the release of preliminary results from an early phase clinical study using patients’ own T cells that have been genetically altered to attack multiple myeloma (MM) cells. Lead investigators for the study presented in three separate sessions at the annual meeting of the American Society of Hematology (ASH).  The initial six patient phase is complete and, based on the encouraging preliminary results, the study was extended to a target enrollment of 26 patients. To date, a total of 15 patients have been enrolled and have received the engineered T cells; of these, 13 have been assessed at day 100 and 11 patients have reached a minimum of six month follow-up for assessment of tumor response to the treatment. Dr. Aaron Rapoport, the Chair of the clinical study, presented abstract 472 entitled “Adoptive Transfer of Gene-Modified T-Cells Engineered to Express High-Affinity TCRs for Cancer Testis Antigens (CTAs) NY-ESO-1 or Lage-1, in MM Patients Post Auto-SCT”. He reports that infusions of engineered T cells have been well tolerated. The overall best response rate at 100 days is 77%, which is encouraging when compared to the rate expected from auto-SCT alone (33%-69% as reported in contemporary published studies). Of the 15 patients treated to date, 10 have ongoing responses, and 5 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 provided the patient’s tumor continues to express target antigen. These infusions will be administered outside of the transplant setting. Dr. Michael Kalos, the lead correlative scientist on the study, presented abstract 755 entitled “Prolonged T Cell Persistence, Homing to Marrow and Selective Targeting of Antigen Positive Tumor in Multiple Myeloma Patients Following Adoptive Transfer of T Cells Genetically Engineered to Express an Affinity-Enhanced T Cell Receptor against the Cancer Testis Antigens.” He reports robust persistence of engineered T cells; in all cases cells are detectable at least six months post infusion, and expression of the engineered TCR on T cells is detected up to one year post infusion. Engineered T cells also traffic to the bone marrow, the site of tumor in MM, and have been detected in the marrow of all patients. The ratio of tumor antigen to tumor cells remains below baseline in all patients, except in cases where loss of engineered T cells occurs. In addition, Dr. Carl June, study sponsor and recipient of the prestigious 2012 Ernest Beutler Award for major translational advances, also presented a summary of the study findings at the Beutler Lecture today. “This study is an important contribution to a growing field of genetic therapies showing exciting promise both as a therapy for myeloma patients and also patients with other hematological and solid malignancies,” states Dr. June. Enrollment is expected to complete in Q2 2013, with 9 month follow-up and final study analysis completed by Q1 2014. A second early phase study, designed to evaluate the safety and anti-tumor effect of the engineered T cells outside of the transplant setting, is expected to open in Q2 2013. * On November 16, 2012, Adaptimmune has announced the publication of dual abstracts in Blood, which report preliminary results from an early phase study using patients’ own T cells that have been genetically altered to attack multiple myeloma cells.  The initial six patient phase is complete and patients have reached a minimum of six month follow-up for assessment of tumor response to the treatment. Based on the encouraging preliminary results, which will be reported at the conference, the study has been extended to a target enrollment of 26 patients. To date, infusion of modified T cells have been well tolerated. The data to be reported at the ASH meeting demonstrates prolonged persistence of modified T cells, homing of the cells to marrow (the site of tumor), and suggests anti-tumor activity. The clinical trial includes patients who have received prior treatment for their myeloma or who have disease considered to be high risk, and who are eligible for an autologous stem cell transplant (auto-SCT). • On May 26, 2011, Adaptimmune has announced that is 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 .

Is general: Yes