Outcomes and assessments
PD, death, Tumor, toxicities
HYPOPHOSPHATEMIA, SEROUS RETINAL DETACHMENT, TUMOR, ADVERSE EVENT, DISEASE, SECONDARY, ADVERSE EVENT, HYPERPHOSPHATEMIA
The primary endpoint was PK/PD characteristics of pemigatinib. For assessment of PK characteristics, plasma samples were collected from all the patients at before each pemigatinib administration on days 1, 2, 8, 14, 15, and 16 during cycle 1, and immediately after, and 0.5 h ± 2 min, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 30 min, and 8 h ± 30 min after each pemigatinib administration on days 1 and 14 during cycle 1. Plasma pemigatinib concentrations were measured using the validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. LC–MS/MS analysis for pemigatinib was carried out with a Sciex API 4000 mass spectrometer, coupled with an HPLC pump and an autosampler. PK parameters for evaluation included maximum serum concentration (CSerum phosphate level was defined as the PD marker in the study for assessing FGFR inhibition. Serial blood samples were collected at before each pemigatinib administration on days 1, 2, 8, and 15 during cycle 1. Serum phosphate levels were measured using phosphomolybdate UV method (measuring range: 0.31‑20.0 mg/dL) by the central laboratory (Q2 Solutions [Beijing] Co., Ltd.).The secondary endpoints were safety and efficacy including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS; duration between the first dosing of pemigatinib and the first documented progressive disease or death). Tumor was assessed per RECIST v1.1 by investigator at baseline, and every 9 weeks after first dosing. Safety was monitored up to 30 days after discontinuation of pemigatinib treatment. Adverse events (AEs) were graded per CTCAE v5.0. Treatment-emergent AEs (TEAEs; defined as an adverse event that emerged or worsened from first dosing to 30 days after pemigatinib treatment discontinuation) are reported. Sponsor-defined clinically notable TEAEs included hyperphosphatemia, hypophosphatemia, nail toxicities, and serous retinal detachment.