On January 8, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported initial safety data from its two ongoing pilot studies of SPEAR T-cells targeting MAGE-A10, one in non-small cell lung cancer (NSCLC) and a triple tumor study in bladder, melanoma, and head & neck cancers (Press release, Adaptimmune, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325398 [SID1234522943]).

To date, 8 patients have each received 100 million transduced MAGE‑A10 SPEAR T-cells in the first dose cohorts of both studies. No evidence of toxicity related to off-target binding or alloreactivity has been observed. There have been no reports of neurotoxicity safety events similar to CAR‑T cell-related encephalopathy syndrome (CRES)1. In the NSCLC study, there has been one serious adverse event of cytokine release syndrome (CRS), a Grade 4 event that resolved with treatment. This event led to cohort 1 expansion from 3 to 6 patients. No dose limiting toxicities were observed in cohort 1 of the triple tumor study.

Following review by the independent safety review committee (SRC), the decision has been made to escalate to the next dose of 1 billion transduced MAGE-A10 SPEAR T-cells in the triple tumor study. This was the therapeutic threshold dose observed with SPEAR T‑cells targeting NY-ESO in the synovial sarcoma pilot study. The decision to escalate in the NSCLC cohort will be reviewed by the SRC following dosing of the 6th patient.

"These safety results, with one of our wholly-owned SPEAR T-cell treatments, and the upcoming escalation to the next dose in the triple tumor study are significant as they allow us to progress treating patients in these studies at a potentially active cell dose," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "As data accumulate throughout 2018, we will continue to share meaningful safety and efficacy data from the MAGE-A10 and MAGE-A4 programs at relevant scientific venues."

Details about Ongoing Trials with SPEAR T-cells Targeting MAGE-A10
There are two ongoing clinical trials with SPEAR T-cells targeting MAGE-A10; one in non-small cell lung cancer (NSCLC), and a triple tumor study in bladder, melanoma, and head & neck cancers. Both studies are dose escalation trials that evaluate three doses of transduced SPEAR T-cells, administered after a lymphodepleting chemotherapy regimen. The three doses being evaluated are 100 million, 1 billion and 1 to 5 billion transduced SPEAR T-cells.

NSCLC study: In this study, five patients have received SPEAR T-cells in the first group of Cohort 1 (1a without fludarabine) 2, and there was one report of Grade 4 CRS that resolved with treatment.

Triple Tumor Study: Three patients have been dosed in the first cohort. There were no reports of CRS greater or equal to Grade 3, and all cases resolved with supportive treatment.