DISCUSSION
nausea, DLTs, diarrhea, stomatitis, fatigue, toxicities, appetite, tumors, TEAEs, cancer, constipation, dysgeusia, alopecia, dry mouth
SEROUS RETINAL DETACHMENT, STOMATITIS, CANCER, DISEASE, TUMORS, SOLID TUMORS, DISORDERS, HYPERPHOSPHATEMIA, EVENTS, ALOPECIA, HYPERPHOSPHATEMIA, DRY MOUTH
In this study, no DLTs were observed and the MTD of pemigatinib was not reached. Safety, tolerability, and PK data supported the selection of 13.5 mg as the RP2D and this was the starting dose for Part 2 of this study. The safety, and PK and pharmacodynamics profiles of pemigatinib in Japanese patients with advanced solid tumors are similar to that observed in patients in the United States and Denmark in the FIGHT‐101 study.The most common (>30%) TEAEs were consistent with on‐target effects of FGFR pathway inhibition and/or conditions associated with underlying disease, and included hyperphosphatemia, dysgeusia, stomatitis, alopecia, decreased appetite, diarrhea, nausea, and constipation. In general, the incidence of any grade TEAEs was higher among patients receiving CD compared with ID schedules. These results are consistent with results reported in the FIGHT‐101 study in patients from the United States and Denmark. The most common (>30%) overall TEAEs in FIGHT‐101 were hyperphosphatemia, fatigue, dry mouth, stomatitis, diarrhea, and alopecia, with a higher incidence of TEAEs overall among patients on CD regimen compared with an ID regimen.Hyperphosphatemia is an anticipated on‐target pharmacologic effect of FGFR inhibition.Other events of clinical interest associated with selective FGFR inhibitors include nail and ocular toxicities, including serous retinal detachment.Phase 1 studies of other FGFR inhibitors in Japanese patients have reported similar AE profiles as reported in our study.In a global phase 1 study of infigratinib, a selective FGFR1‐3 inhibitor, the most commonly reported (>30%) TEAEs were hyperphosphatemia, constipation, appetite decreased, stomatitis, diarrhea, nausea, and fatigue. Other toxicities associated with selective FGFR pathway inhibition such as eye‐related disorders were also reported in infigratinib‐treated patients.Following a single dose of pemigatinib 9 or 13.5 mg QD, plasma concentrations of pemigatinib remained at or above the in vivo ICPlasma FGF23 was used as a prespecified marker for Efficacy analyses demonstrated clinical activity with five PRs reported across tumors in patients receiving pemigatinib 13.5 mg QD in Part 2 including one receiving ID and four receiving CD. All of the five patients had This study had limitations that are common for phase 1/2 studies. No statistical comparisons across dosing regimens or cancer types were planned. Therefore, the study was not sufficiently powered for such comparisons. Only a small number of patients with a variety of solid tumors were enrolled.