In his discussion, Dr. Herbst commented that the part A results “look okay, until you realize that the most of the activity is in those patients who are T790M-positive, who have not been exposed in this cohort to a third-generation T790M inhibitor.” Patients with the mutation who are treated with third-generation inhibitors would be expected to have a 78% response rate.
Part B included a few more patients with responses who were negative for T790M. “My thought here is that perhaps there is a biomarker” for selecting patients most likely to benefit from the combination, he said.
For MET-negative patients, the combination appears to have manageable toxicities with noncontinuous dosing of selumetinib, and there may be benefit to using it in the first-line setting in select patients, but that will require further trials and identification of suitable biomarkers, Dr. Herbst summarized.
TATTON was sponsored by AstraZeneca. Dr. Ramalingam reported receiving research support from the company and consulting/contracting with others. Dr. Herbst reported receiving research support from AstraZeneca, Eli Lilly, and Merck, and serving as a consultant for AstraZeneca, Eli Lilly, Genentech/Roche, Merck, NextCure, and Pfizer.
SOURCE: Ramalingam SS et al. AACR 2019,