Exposure-response analyses of pemigatinib in patients with myeloid/lymphoid neoplasms with fibroblast growth factor receptor 1 rearrangement

Pemigatinib is a selective, potent, orally administered inhibitor of fibroblast growth factor receptor (FGFR)1-3 with antitumor activity in multiple solid tumors. Pemigatinib is used to treat adults with previously treated metastatic or surgically unresectable cholangiocarcinoma with <i>FGFR2</i> alterations, as well as adults with relapsed or refractory myeloid/lymphoid neoplasm (MLN) with an <i>FGFR1</i> rearrangement (MLN-<i>FGFR1</i>). Data from recent clinical studies were used to develop pemigatinib exposure-response models for patients with MLN-<i>FGFR1</i> and to evaluate the impact of pemigatinib exposure on efficacy and safety. The degree of pemigatinib exposure did not predict the level of efficacy in patients with MLN-<i>FGFR1</i> in this analysis. Pemigatinib exposure was a significant predictor of the frequency of clinically relevant treatment-emergent adverse events. The estimated probabilities of developing hyperphosphatemia, dry mouth, nail toxicity, alopecia, stomatitis, and diarrhea were higher with a continuous dosing schedule versus an intermittent dosing schedule.