FDA Accepts Adaptimmune’s IND Application for 3rd SPEAR T-cell Therapy

FDA Accepts Adaptimmune’s IND Application for 3rd SPEAR T-cell Therapy

The U.S. Food and Drug Administration has accepted Adaptimmune Therapeutics‘ investigational new drug (IND) application for genetically modified T-cells that recognize the MAGE-A4 protein in patients with multiple solid tumors. Adaptimmune will now move this therapy into clinical trials.

The IND filing for MAGE-A4 was supported by preclinical data presented at the Society for Immunotherapy of Cancer (SITC) 2016 annual meeting Nov. 9-13 in National Harbor, Maryland.

The poster presentation, titled “Preclinical evaluation of an optimal-affinity MAGE-A4 T-cell receptor for adoptive T-cell therapy,” revealed the strong cytotoxicity of this therapy against MAGE-A4-positive melanoma and non-small cell lung cancer (NSCLC) cell lines, without major safety concerns, as assessed using Adaptimmunes’s preclinical lab culture testing system.

MAGE-A4 is a very attractive target because in adults it is restricted to the testis, but is found at high levels in several tumor types, including NSCLC, melanoma, bladder, head and neck, esophageal, and gastric cancers.

Now, Adaptimmune will initiate a Phase 1, open-label, dose-escalation study assessing the maximum tolerated dose, safety, and effectiveness of MAGE-A4 SPEAR T-cell therapy in HLA*02-positive patients who have inoperable locally advanced or metastatic NSCLC, or melanoma, head and neck, ovarian, urothelial and gastric cancers that express the MAGE-A2 protein.

The study will enroll up to 32 patients who will first be treated with a modified Fludara (fludarabine) and cyclophosphamide chemotherapy, as used in the company’s synovial sarcoma study.

Using its SPEAR (specific peptide enhanced affinity receptor) T-cell platform, the company uses the patient’s own T-cells and engineers them to express a T-cell receptor with a high affinity for specific cancer proteins.

In addition to SPEAR T-cell therapy targeting MAGE-A4, Adaptimune has two other wholly-owned therapeutic candidates in clinical trials: the NY-ESO SPEAR T-cell therapy and the MAGE-A10 SPEAR T-cell therapy, both of which have been showing signs of safety and effectiveness in Phase 1/2 trials in both solid tumors and hematological cancers.

The NY-ESO SPEAR T-cells, in particular, were still detectable in the blood of a synovial sarcoma patient 28 months after infusion, without becoming exhausted. These cells retained their anti-tumor activity against NY-ESO-positive cells without additional re-estimulation.