Study reports encouraging response rate and safety profile
(Oxford, UK and Philadelphia, PA, 17 October, 2014). Adaptimmune Limited, a leading biotechnology company focused on the use of T-cell therapy to treat cancer and infectious disease, today announces the release of interim results from a pilot clinical trial 04511 of NY-ESOc259T which uses a patient's own T cells that have been genetically altered to attack synovial sarcoma cells.
The preliminary results, presented by the study investigator for the first time today at the Connective Tissue Oncology Society's (CTOS) annual meeting in Berlin, demonstrate an 80% response rate and excellent safety profile.
The clinical trial at the National Cancer Institute (NCI) in Maryland, Memorial Sloan Kettering in New York, and Children's Hospital of Philadelphia in Philadelphia, is currently designed as a 10 patient single arm open label study in patients with synovial sarcoma that is unresectable, metastatic or recurrent. The patients are given four days of preparatory chemotherapy followed two days later by an infusion of NY-ESOc259T - their own T cells that have been genetically engineered to carry receptors that help the T cells recognize and attack tumors, while sparing healthy tissue.
To date, eight patients have received infusions of engineered T cells which have been well tolerated. Two patients were diagnosed with mild (grade 1 or 2) cytokine release symptoms, which often correlated with tumor flare and production of interleukin 6 (IL-6) and interferon gamma (IFN-γ). Currently, five have reached the 60 day time point for assessment of clinical response. Altogether, four of these five patients (80%) have responded, with one complete response (up to 9 months), and three partial responses (up to 9, 6, and 4 months). The three patients experiencing partial responses all underwent surgical resection of their remaining detectable lesion. Overall survival rates will be collected as the study follow-up matures.
Based on the encouraging results, the protocol will be extended to include an additional 30 patients. The extension will utilize cell product produced using a commercially compliant manufacturing process that will be in place by early 2015 and will also evaluate a simplified preparatory chemotherapy regimen.
Adaptimmune is co-developing NY-ESOc259T under the terms of a strategic cancer immunotherapy partnership with GlaxoSmithKline (GSK) announced in June. Under the terms of the agreement, GSK has an option on the programme through to clinical proof of concept and upon exercise will assume full responsibility for commercializing the programme.
"The clinical responses seen in our patients are encouraging and the data suggest that responses to T cell therapy in this population are possible without the use of systemic IL-2," says Dr. Tom Holdich, Medical Director at Adaptimmune. "The responses observed in our patients so far represent an alteration in the expected natural course of the disease. We will continue to gather data on the durability of the therapy in patients with complete responses, or who have been rendered disease free through surgery, but so far the data are encouraging and the safety profile is very good."
"It is a privilege to work with such an outstanding investigational team in the context of such an intractable disease, which particularly affects younger people," said James Noble, Chief Executive Officer of Adaptimmune. "There are still many questions to answer as we build on these early results, and we are hoping to increase enrolment significantly so as to address these for the benefit of patients."
"These preliminary results support the promise of engineered cell therapy for unmet medical needs in oncology. We look forward to the completion of this pilot study early next year, and to expansion of the trial to encompass additional patient cohorts," commented Dr. Elliott Sigal, a Non-Executive Director of Adaptimmune and former Chief Scientific Officer and Executive Vice President of Bristol Myers-Squibb.
NY-ESOc259T study 04511 in synovial sarcoma
Synovial sarcomas account for approximately 6%-10% of all soft tissue sarcomas. Approximately one third of synovial sarcomas occur in childhood and the peak incidence is in the third decade of life, with 70% of sarcomas occurring in patients younger than 40 years. First line therapy typically involves radiotherapy and chemotherapy, and surgical resection where possible. There are limited additional treatment options for unresectable, recurrent and metastatic synovial sarcoma, which is nearly always fatal.
The clinical study focuses on this unmet medical need and includes patients who have received standard first line therapy containing ifosfamide and/or doxorubicin and who are either intolerant or no longer responding to the regimen, and whose tumor expresses NY-ESO-1.
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-1a. Anti-tumor responses are reported in accordance with RECIST criteria monthly post infusion. Patients are also monitored no less than bi-annually for safety and correlatives specific to the engineered T cells. The study is scheduled to complete in early 2015.
A similar earlier clinical study in synovial sarcoma, also carried out at the NCI, was reported in the Journal of Clinical Oncology in 2011. The study used Adaptimmune's NY-ESO TCR, but employed an older cell manufacturing method and required supportive IL-2 injections. The study reported encouraging activity with clinical responses in 4 of 6 patients treated.
The study reported at CTOS uses a similar clinical design, but employs an updated rapid manufacturing method and does not require IL-2 injections. A key aim of this pilot study was to establish whether similar responses could be achieved without the use of systemic IL-2.
The study was originally developed by Dr. Crystal Mackall and Dr. Carl H. June at the University of Pennsylvania Abramson Cancer Center. Dr. Mackall is the protocol Chair and works closely with Dr. Melinda Merchant for carrying out the protocol at the NCI. Dr. Merchant is the leading Associate Investigator for the study, and a Staff Clinician at the Pediatric Oncology Branch at the NCI. Dr. Merchant today presents paper 026 entitled "Genetically Engineered NY-ESO-1 Specific (c259) T Cells in HLA-A2+ Patients with Synovial Sarcoma".
Other investigators on the study include Dr. William Tap and Dr. Sandra D'Angelo at Memorial Sloan Kettering Cancer Center, and Dr. Stephen Grupp at the Children's Hospital of Philadelphia. In April 2013, Adaptimmune assumed the sponsorship and T cell manufacturing roles for this study from the University of Pennsylvania. Adaptimmune is also the financial sponsor for the study and owns the T cell receptor technology.
Interim results for NY-ESOc259T in a study in multiple myeloma (clinicaltrials.gov identifier NCT01892293) also showed a favorable response rate and safety profile, as reported previously at the American Society of Hematology in December 2013 (77% complete response rate in 20 patients at 100 days post-infusion of the modified cells).
Additional study details and contact information for patients interested in finding out more about participation can be found at https://clincialtrials.gov, under trial identifier number NCT01343043. Other trials of NY-ESOc259T in ovarian cancer, melanoma, and myeloma are ongoing in the U.S. and can be found at clincialtrials.gov. A study in non-small cell lung cancer is planned for mid-2015.
Study reports encouraging response rate and safety profile