JIH-HSIANG LEEWEI-WU CHENCHIH-HUNG HSUYen Y.-H.CHIH-HSIN YANGANN-LII CHENGSasaki S.-I.Chiu L.Y.Sugihara M.Ishizuka T.Oguma T.Tajima N.CHIA-CHI LIN2020-04-282020-04-2820200167-6997https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062708549&doi=10.1007%2fs10637-019-00745-z&partnerID=40&md5=ac9be5f41e6978f5292b125c55a1a7cbhttps://scholars.lib.ntu.edu.tw/handle/123456789/487249Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600?mg/d; cohort 2, 1000?mg/d for 2?weeks, then 800?mg/d. Primary objectives assessed pexidartinib safety and tolerability, and determined the recommended phase 2 dose; secondary objectives evaluated efficacy and pharmacokinetic profile. Results All 11 patients (6 males, 5 females; median age 64, range 23–82; cohort 1 n = 3; cohort 2 n = 8) experienced at least one treatment-emergent adverse event; 5 experienced at least one grade ? 3 adverse event, most commonly (18%) for each of the following: increased aspartate aminotransferase, blood alkaline phosphatase, gamma-glutamyl transferase, and anemia. Recommended phase 2 dose was 1000?mg/d for 2?weeks and 800?mg/d thereafter. Pexidartinib exposure, area under the plasma concentration-time curve from zero to 8?h (AUC0-8h), and maximum observed plasma concentration (Cmax) increased on days 1 and 15 with increasing pexidartinib doses, and time at Cmax (Tmax) was consistent throughout all doses. Pexidartinib exposure and plasma levels of adiponectin and colony-stimulating factor 1 increased following multiple daily pexidartinib administrations. One patient (13%) with tenosynovial giant cell tumor showed objective tumor response. Conclusions This was the first study to evaluate pexidartinib in Asian patients with advanced solid tumors. Pexidartinib was safe and tolerable in this population at the recommended phase 2 dose previously determined for Western patients (funded by Daiichi Sankyo; clinicaltrials.gov number, NCT02734433). ? 2019, The Author(s).[SDGs]SDG3adiponectin; alkaline phosphatase; aspartate aminotransferase; bilirubin; colony stimulating factor 1; gamma glutamyltransferase; pexidartinib; aminopyridine derivative; CSF1R protein, human; granulocyte macrophage colony stimulating factor receptor; pexidartinib; pyrrole derivative; tumor marker; adult; aged; anemia; area under the curve; Article; Asian; backache; cancer patient; clinical article; cohort analysis; diarrhea; disease exacerbation; drug blood level; drug dose escalation; drug efficacy; drug safety; drug tolerability; fatigue; female; hair color; human; hypertransaminasemia; male; maximum concentration; open study; pharmacodynamics; phase 1 clinical trial; priority journal; solid malignant neoplasm; clinical trial; controlled clinical trial (topic); follow up; maximum tolerated dose; metabolism; middle aged; neoplasm; pathology; prognosis; tissue distribution; very elderly; young adult; Adult; Aged; Aged, 80 and over; Aminopyridines; Biomarkers, Tumor; Female; Follow-Up Studies; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Non-Randomized Controlled Trials as Topic; Prognosis; Pyrroles; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Tissue Distribution; Young Adultjournal article10.1007/s10637-019-00745-z308251042-s2.0-85062708549