Clinical Trials

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: SPEAR® T-Cell Therapy Targeting NY-ESO-1

Action mechanism:

• cell therapy/immunotherapy product/gene therapy Autologous T-cells have been genetically engineered with an enhanced affinity NY-ESO-1 T-cell receptor in ovarian cancer patients with the HLA-A*0201, HLA-A*0205, and/or HLA-A*0206 allele and whose tumor expresses the NY-ESO-1 tumor antigen. Though the prevalence of HLA sub-types varies from population to population, the most common in the western world is HLA-A2. Among the HLA-A2 variants, the most prevalent are HLA-A*0201 and HLA-A*0206.

Disease: recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum-resistant disease expressing NY-ESO-1

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

• This study, will take a subject's "T cells" and "teach" them to be able to recognize and attack the ovarian cancer cells. This is done by putting in a gene or genetic material that will change how a subject's T cells work and hopefully get them to attack and kill ovarian cancer cells. For subjects who have the HLA A2 tissue-type marker, the T cells would be engineered to recognize a substance called "NY-ESO-1". After putting this new gene in T cells  the investigators will grow the cells in the laboratory and give these cells back to subjects. (NCT01567891)

Latest news:

• • On June 5, 2017, Adaptimmune announced a poster presentation on updated data from its clinical trial evaluating NY-ESO SPEAR T-cells in patients with ovarian cancer at the American Society of Clinical Oncology (ASCO) Annual Meeting. Subjects must be = 18 years old; HLA-A*02:01, *02:05, or *02:06 positive; have recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum-resistant disease expressing NY-ESO-1 at =1+ intensity in =10% of tumor cells by IHC; have measurable disease; have ECOG status 0 or 1; and have adequate organ function. The study evaluates two lymphodepleting regimens: cyclophosphamide alone (enrollment completed; n=7) and cyclophosphamide plus fludarabine (up to 10 subjects to be treated). The first 6 subjects were lymphodepleted prior to T-cell infusion with various regimens of cyclophosphamide alone. The target dose is of 1 – 6 ×10⁹ transduced SPEAR T-cells. Enrollment is ongoing.
• • On October 12, 2016, Adaptimmune Therapeutics announced that its amended protocol using its NY-ESO SPEAR® (Specific Peptide Enhanced Affinity Receptor) T-cell therapy in ovarian cancer patients with treatment resistant or refractory metastatic ovarian cancer is now actively recruiting. To date, no objective clinical responses have been reported in the ovarian cancer patients who received NY-ESO SPEAR T-cell therapy in the initial iteration of this trial. Of note, these initial patients received a preconditioning regimen which consisted of cyclophosphamide alone, rather than including fludarabine. Data from Adaptimmune’s studies of its NY-ESO SPEAR T-cell therapy in synovial sarcoma patients have indicated the importance of including fludarabine in the preconditioning regimen. The use of fludarabine appears to be required for expansion, response and persistence of transduced cells. As a result, this trial will enroll patients under a revised protocol including a pre-conditioning regimen that includes fludarabine in combination with cyclophosphamide.
• This multi-center study is intended to enroll up to 10 additional patients under the revised protocol, and will assess the safety and tolerability of Adaptimmune’s NY-ESO SPEAR T-cell therapy in patients with treatment resistant or refractory metastatic ovarian cancer expressing the NY-ESO-1 antigen. Secondary objectives will include the assessment of clinical efficacy, measurements of durability of persistence of NY-ESO SPEAR T-cells in the blood, and exploratory tumor biomarker studies, and evaluations of the phenotype and functionality of NY-ESO-1 SPEAR T-cells.
• • On July 25, 2013, Adaptimmune has announced that it has opened a Phase I/IIa, multiple-site, two-cohort, open-label clinical trial in ovarian cancer at Roswell Park Cancer Institute (RPCI) in Buffalo, N.Y., and City of Hope (COH) in Duarte, Calif. Researchers will investigate the safety, bioactivity and effectiveness of treating patients with their own T cells after genetically engineering the cells to enhance their antitumor properties.
• During the trial, T cell receptors (TCRs) that have been developed using Adaptimmune’s unique TCR enhancement technology will be deployed to target two CT antigens, NYESO-1 and LAGE-1. They will be transferred to the patients’ T cells in a process for autologous T cell manufacturing developed by Carl June, MD, and Bruce Levine, PhD, at the Perelman School of Medicine at the University of Pennsylvania, Pa., and then licensed to Adaptimmune. Manufacturing will be performed centrally by Progenitor Cell Therapy in Allendale, N.J. Adaptimmune is the regulatory sponsor, owns the core T cell receptor technology, and is funding the study. Dr. Odunsi is the lead clinical investigator at RPCI and protocol Chair. Mihaela Cristea, MD, associate clinical professor, Medical Oncology, is the lead clinical investigator at City of Hope.
• The study is opening on the heels of promising clinical data emerging in sarcoma and myeloma studies, where the same engineered T cell product is under investigation. Interim data from these studies was presented at the American Association for Cancer Research Annual Meeting in March and American Society for Cell and Gene Therapy Annual Meeting in May.
• Infusion of the CT antigen-specific T cells will occur following a brief treatment with relatively high dose of “lymphodepleting” chemotherapy to prepare the patient’s immune system for the gene-modified T cells. Previous clinical trials for different cancer indications have demonstrated that the lymphodepleting chemotherapy procedure is safe and promotes reconstitution of the immune system with the gene-modified T cells.

Is general: Yes