Adaptimmune presents clinical results of NY-ESO TCR therapeutic candidate at ASCO 2015

Adaptimmune Therapeutics plc (Nasdaq: ADAP), a clinical stage biopharmaceutical company focused on the use of TCR engineered T-cell therapy to treat cancer, today announced a poster presentation of data on its lead clinical program, an affinity enhanced T-cell receptor (TCR) therapeutic targeting the NY-ESO-1 cancer antigen, in both solid and hematologic cancers. Eighty-two (82) patients have been treated to date with NY-ESO-T; 44 under Adaptimmune’s IND, and 38 under a National Cancer Institute IND (Robbins et al., CCR, 2014). The data from Adaptimmune’s clinical studies in synovial sarcoma, multiple myeloma and ovarian cancer were presented at the 2015 Annual American Society of Clinical Oncology (ASCO) Meeting.

In this poster presentation, entitled: "Genetically Engineered NY-ESO-1 Specific T-Cells in HLA-A201+ Patients with Advanced Cancers," Melinda Merchant, M.D., Ph.D., Clinical Director of the Pediatric Oncology Branch of the National Cancer Institute, National Institutes of Health, in Bethesda, MD described the early clinical experience of the NY-ESO TCR therapeutic (NY-ESO-T) in 44 patients across indications.

The authors of the poster concluded:

  • NY-ESO-T demonstrated robust clinical responses in solid and hematologic tumors, including a 60 percent (6/10) confirmed response rate in synovial sarcoma, and a 59 percent (13/22) response rate (Complete Response + near Complete Response, per International Myeloma Working Group guidelines) in myeloma in the context of autologous stem cell transplant. Approximately 62 percent (8/13) of responders had tumors with abnormal cytogenetics; 4/8 of these abnormalities are associated with high risk disease.
  • In addition, a response was seen in an initial ovarian patient and patient’s tumor markers were observed to be falling during this period of response. The response was abrogated by the use of systemic steroids to treat cytokine release syndrome. Reduction in pre-conditioning chemotherapy intensity in the subsequent four ovarian patients was associated with short T-cell persistence and lack of a meaningful antitumor effect. New studies are being conducted to identify the optimal dosage of pre-conditioning chemotherapy for NY-ESO-1 T-cell function.
  • Durability of response ranged from 2 to 9 months, and from 3 months to ongoing response at 2.5 years in the sarcoma and myeloma studies respectively.
  • NY-ESO-T has been generally well-tolerated with no long term side-effects detected to date. In the 44 patients treated under the Adaptimmune IND, the most common adverse events include diarrhea, pyrexia, and fatigue. Grade 3 cytokine release syndrome was observed in two patients, which was manageable with supportive care measures and resolved without sequelae.
  • Importantly, NY-ESO-1 T-cells exhibited durable persistence without the requirement for IL-2 support in vivo, and cells were detectable for up to three years in peripheral blood by PCR. Additionally, the data show continued expression of the NY-ESO TCR for up to two years and continued NY-ESO-T function in a subset of patients, without accumulation of multiple exhaustion markers. NY-ESO-T memory phenotype is generated in persisting cells suggesting the programming of immunological memory for NY-ESO-T.

Dr. Rafael Amado, Adaptimmune’s Chief Medical Officer, said;

These results - in particular the response rate in a solid tumor setting and the immune correlates of NY-ESO-T persistence, function, and the absence of T-cell exhaustion - represent important fundamental findings heretofore not observed in the field of T-cell receptor gene therapy for cancer. The data support the promise of our engineered T-cell platform as a means of augmenting a patient’s immune system to fight cancer, and provide a rationale for the clinical development of additional TCR specificities across a spectrum of tumor types. We look forward to building on these findings to develop TCR-based therapeutics which may one day offer an important treatment option to patients with diverse solid and hematologic malignancies.

Data from the multiple myeloma and synovial sarcoma clinical studies were initially presented on April 21 at the 2015 annual meeting of the American Association for Cancer Research (AACR) in Philadelphia, PA by lead principal investigators, Aaron Rapoport, M.D., Professor of Medicine and Director of Lymphoma Gene Medicine, Marlene and Stewart Greenebaum Cancer Center (AACR abstract number 4701), and Dr. Merchant (AACR abstract number 4707).  

Adaptimmune’s NY-ESO TCR therapeutic candidate is a novel cancer immunotherapy that has been engineered to target and destroy cancer cells by strengthening a patient’s natural T-cell response. T-cells are a type of white blood cell that play a central role in a person’s immune response. Adaptimmune’s goal is to harness the power of the T-cell and, through its NY-ESO TCR therapeutic candidate, significantly impact cancer treatment and clinical outcomes of patients with cancers, including synovial sarcoma, multiple myeloma, melanoma, ovarian cancer, lung cancer and esophageal cancer.

Source: http://www.adaptimmune.com/

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