Date: 2017-06-05
Type of
information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Adaptimmune (UK)
Product: NY-ESOc259T cell therapy product
Action
mechanism:
- cell therapy/T cell receptor T cell therapy/gene therapy/immunotherapy product. Using its T-cell receptor (TCR) engineering technology, Adaptimmune has created TCRs which are deployed to target the cancer testis antigen, NY-ESO-1, and other targets. The company’s trials in the NY-ESO-1 programme in multiple myeloma, melanoma, sarcoma and ovarian cancer in the US are generating encouraging results, with European trials set to commence shortly, and it has a pipeline of follow-on programmes.
Disease: synovial sarcoma
Therapeutic
area: Cancer Oncology
Country: USA
Trial
details:
- • On July 25, 2011, Adaptimmune announced that up to 10 patients will be enrolled in the trial, which may take up to three years to accrue due to the rare nature of the cancer. In addition to evaluating safety, the primary objective of the study is to determine the response rate to the therapy. Secondary endpoints are to investigate the persistence of the genetically modified cells and to perform analyses of the anti-tumor immune responses in patients. (NCT01343043)
- In this clinical trial at the National Cancer Institute (NCI) in Maryland, Memorial Sloan Kettering in New York, and Children’s Hospital of Philadelphia in Philadelphia, 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.
- 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.
Latest
news:
- • On June 5, 2017, Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center presented an update on all cohorts from Adaptimmune's NY-ESO study in synovial sarcoma at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago (“Open label, non-randomized, multi-cohort pilot study of genetically engineered NY-ESO-1 specific NY-ESO-1c259t in HLA-A2+ patients with synovial sarcoma”).
- NY-ESO continues to be generally well-tolerated and initial anti-tumor activity has been observed in all ongoing cohorts including low expressors of NY-ESO (Cohort 2).
Of the twelve patients treated in Cohort 1 (non-modified fludarabine / cyclophosphamide lymphodepletion regimen), five remain alive with a median predicted overall survival of 120 weeks (~28 months) (data cutoff March 30, 2017)
- Confirmed responses have been observed in all cohorts as follows:
- — Cohort 1 (High Flu/Cy, High NY-ESO): 6/12 (50%) patients with a median progression free survival (PFS) of 15 weeks (range:8, 38); 6/10 (60%) response rate in patients who received a target dose of at least one billion cells
- — Cohort 2 (High Flu/Cy, Low NY-ESO): 2/5 (40%); ongoing
— Cohort 3: (High cyclophosphamide, no fludarabine, High NY-ESO): 1/5 (20%); cohort closed
- — Cohort 4 (Modified Flu/Cy, High NY-ESO): 3/6 (50%); (ongoing)
- Peak and long-term expansion of NY-ESO SPEAR T-cells appears to correlate with clinical efficacy. Fludarabine appears to be an important component of the lymphodepletion regimen. All reported events of cytokine release syndrome resolved with supportive care, and the majority of events were Grade 1 or 2. There were no reported events of seizure, cerebral edema, or encephalopathy.
- • On September 1, 2015, Adaptimmune announced that the first patient has been dosed in its expanded Phase I/II trial of its affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen in synovial sarcoma patients. Based on encouraging results in the first cohort of 10 patients, presented at the American Association for Cancer Research (AACR) annual meeting in April 2015, the trial is being expanded to encompass an additional 20 patients in two further cohorts. The expansion of Adaptimmune’s trial also triggers two milestone payments from GSK. Adaptimmune is collaborating with GSK for the development of its NY-ESO TCR program through a strategic cancer immunotherapy partnership announced in June 2014. Under the terms of the agreement, GSK has an exclusive option to license Adaptimmune’s NY-ESO TCR therapeutic and upon exercise would assume full responsibility for further development and commercialization of the therapeutic.
- Adaptimmune’s clinical study includes synovial sarcoma patients who have received standard first line therapy containing ifosfamide and/or doxorubicin and who are intolerant or no longer responding to the regimen, and whose tumor expresses a tumor antigen known as NY-ESO-1. The NY-ESO-1 antigen is believed to be present in 60 to 70 percent of synovial sarcoma patients. The primary objectives of the study are to determine the safety of adoptively transferred autologous T cells expressing an affinity enhanced T cell receptor that recognizes the NY-ESO-1 antigen in HLAA*0201, HLA-A*0205, and/or HLA-A*0206 positive patients with unresectable, metastatic or recurrent synovial sarcoma. Secondary objectives include the determination of efficacy through response rate and duration of response.All eligible patients will be treated with lymphodepletive chemotherapy followed by administration of Adaptimmune’s NY-ESO TCR therapeutic. In the first cohort, patients whose tumor expressed NY-ESO-1 at high levels received a single course of cyclophosphamide and fludarabine for lymphodepletion prior to administration of Adaptimmune’s NY-ESO TCR therapeutic. Cohort 2 will enroll patients whose tumor expresses lower levels of the NY-ESO-1 antigen and who will receive the same treatment as patients in the first cohort. Cohort 3 will enroll patients whose tumor expresses high levels of the NY-ESO-1 antigen and will study the removal of fludarabine as part of the lymphodepletion regimen. Both cohorts are expected to open concurrently.
• On October 17, 2014, Adaptimmune announced 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. 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-?). 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 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.
Is
general: Yes
