Pharmacodynamics
NSCLC, non-small cell lung cancer
NON-SMALL CELL LUNG CANCER, NSCLC
Paired biopsy analysis was achieved for one patient with NSCLC with a MET exon 14 skipping mutation, dosed with 200 mg BID. The on-treatment biopsy showed a near-complete inhibition of phosphorylated MET, without affecting total MET levels (Total and phosphorylated MET assessment with immunohistochemistry on paired biopsy samples of a patient with MET exon 14 mutated non-small cell lung cancer dosed at 200 mg BID.Mean creatinine levels were higher than baseline for all patients in all cohorts at all time points measured throughout the study (ranging from 6.6% to 121.5% increase from baseline), in keeping with on-target OCT-2 inhibition; however, throughout the study, overall mean creatinine levels were within the normal ranges and changes in mean creatinine levels over time were lowest in cohort 1 (100 mg BID).Plasma tryptophan and kynurenin levels on cycle day 1 at pre-dose and 8 h first post-dose were available for 30 patients in Module 1. A significant increase in mean tryptophan plasma levels on cycle 1 day 1 was seen between pre-dose samples and 8 h post-dose samples (9475 ng/mL vs. 10 605 ng/mL, 95% CI [247.622, 2011.871], A decrease in mean kyn/trp ratio was seen between pre-dose samples and 8 h post-dose samples (57 vs. 49 resp, CI 95% [4.1738-11.3506], 