Adaptimmune’s dose escalation strategy for lead MAGE-targeted TCR cancer therapies has nebulous efficacy value; prior data has interpretation limitations, experts say

31 Jul 2019

Boosting the number of cells in Adaptimmune Therapeutics’ (NASDAQ:ADAP) lead T-cell receptor (TCR) therapies in ongoing Phase I oncology trials is unlikely to form the basis of enhancing its efficacy potential, experts said. While there is early positive data for both ADP-A2M4 (formerly MAGE-A4 TCR) and ADP-A2M10 (formerly MGE-A10 TCR), interpreting results across tumor types is challenging, they noted.

It is possible that the dosing requirement for TCR therapy will be handled on a case-by-case basis based on the tumor type and individual patient, an expert said. While an analyst report states a dose of more than 10 billion cells may be important for efficacy based on initial data in synovial sarcoma, interviewed experts explained the dose-response curve may not be so clear. The rationale behind simply increasing the dose could be due to the lack of understanding which cancer cells are relevant, and an exponential dose-response curve should not be expected, experts noted.

Overall efficacy forecasts are also challenging, experts said, even though they were encouraged by the early synovial sarcoma data. Extrapolation to solid tumors is not appropriate, three experts said, although one noted it is nonetheless a positive signal for more immunogenic cancers like melanoma. The solid tumor stable disease (SD) data is hard to interpret, as some tumors are more aggressive or have been exposed to earlier immune system-targeting therapies, experts said.

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