https://www.selleckchem.com/products/jib-04.html In cohort 2 (450 mg BID), we observed no DLTs in 3 patients. Pharmacokinetic analysis revealed that AUC to 600 mg BID was higher than that previously reported in global trials. We determined 450 mg BID as the RD for P2. In 25 RET inhibitor-naïve patients, one achieved an objective response (4%) and 13 achieved disease control at 8 weeks (52%). The median progression-free survival (PFS) was 3.4 months (95% CI, 2.0-5.4), while the median overall survival was 19.0 months (5.4-NE). We observed grade 3 adverse events (AEs) (4%) including pneumonitis in P2. Alectinib exerts limited activity against -rearranged NSCLC. Further investigation to elucidate the mechanisms underlying sensitivity and resistance of RET inhibitors is required to improve outcomes for these patients. Alectinib exerts limited activity against RET-rearranged NSCLC. Further investigation to elucidate the mechanisms underlying sensitivity and resistance of RET inhibitors is required to improve outcomes for these patients. Metabolic profiling in non-small cell lung cancer (NSCLC) may identify key metabolic vulnerabilities and shows enormous discovery potential. Preclinical studies showed that metabolic rewiring in cancer plays an essential role in modulation of immunotherapy response. However, this situation is understudied in the clinical setting. Therefore, we aimed to evaluate the plasma metabolic profile of immune checkpoint inhibitor (CI) responding versus non-responding NSCLC patients. The aim of this project is to identify potential predictive biomarkers for CI response. Plasma samples from CI treated NSCLC patients were analysed at baseline and at the first follow up scan by using a broad targeted metabolomics mass spectrometry panel, and were compared to healthy controls. For further validation of identified key alterations high-performance liquid chromatography (HPLC) for tryptophan (Trp) and kynurenine (Kyn) as indicator of IDO-activity was perfo