ASCO: Adaptimmune builds case for GlaxoSmithKline-partnered T-cell therapy

Abingdon, close to where Adaptimmune is based. (Motmit/CC BY-SA 3.0)

Adaptimmune has presented updated clinical data on its T-cell therapies. The latest readouts link the GlaxoSmithKline-partnered NY-ESO SPEAR T-cells to a 50% partial response rate in heavily pretreated cancer patients and position Adaptimmune to dial up the dosing of two wholly owned assets.

Oxford, U.K.-based Adaptimmune has the most data on the NY-ESO candidate it is transferring to GSK for further development. Of the eight myxoid/round cell liposarcoma (MRCLS) patients to receive the drug, four have experienced partial responses, one of which is unconfirmed. Three other patients had stable disease.

The response rate has dipped somewhat since earlier in the year, when Adaptimmune reported three of the first four patients to receive the drug had responded. But given the patients have inoperable or metastatic disease that has proved resistant to anthracycline, the proportion of partial responses still suggests the drug may have a future in MRCLS. The big, outstanding question is how durable the responses will be. 

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Adaptimmune also came through the latest update without triggering any alarms on the safety front. The study reported adverse four events linked to the T-cell therapy in three patients. One patient had grade three cytokine release syndrome (CRS) that was resolved after six days. Adaptimmune also saw two grade two cases of CRS and grade two pleural effusion, which may have been caused by the therapy. Earlier updates in gastroesophageal cancer and synovial sarcoma reported treatment-related deaths. 

The lack of such events in the latest MRCLS data was one of a few positive safety readouts released by Adaptimmune at the 2018 ASCO Annual Meeting. The other updates came from clinical trials of MAGE-A10 and MAGE-A4.

Trials of both therapies have administered 100 million cell doses without major incident or evidence of off-target toxicity, encouraging researchers to move up to the 1 billion cell dose. Adaptimmune has dosed a patient with 1 billion cells of MAGE-A4 and is enrolling patients at the dose in the MAGE-A10 trials. 

The step up in dosing should lead to clearer evidence of whether the treatments work. Researchers saw no antitumor effects when they administered 100 million MAGE-A10 cells to patients with non-small cell lung cancer and other solid tumors. The finding is in keeping with the study of the NY-ESO cells in synovial sarcoma. In that case, the 1 billion cell dose was the therapeutic threshold.