Safety
hypophosphatemia, serous retinal detachment, Hypophosphatemia, Hyperphosphatemia, ascites, dyspnea, stomatitis, TEAEs, dry eye, dysgeusia, nausea, fatigue, keratitis, hyperphosphatemia, DLTs, ocular TEAEs, Cholangitis, alopecia, hyperesthesia
HYPOPHOSPHATEMIA, SEROUS RETINAL DETACHMENT, MALIGNANT NEOPLASM PROGRESSION, HYPOPHOSPHATEMIA, EVENTS, HYPERPHOSPHATEMIA, ASCITES, STOMATITIS, PUNCTATE KERATITIS, DRY EYE, ADVERSE EVENTS, METASTATIC BRAIN CANCER, KERATITIS, HYPERPHOSPHATEMIA, ADVERSE EVENT, CHORIORETINOPATHY, EVENT, DISEASE, CHOLANGITIS, ALOPECIA
No DLTs were reported in Part 1 of the study and the MTD of pemigatinib was not reached. Treatment‐emergent adverse events (TEAEs) were experienced by all enrolled patients (Common TEAEs (>5%) and clinically notable TEAEs.
Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; TEAE, treatment‐emergent adverse event; WBC, white blood cell.In general, the incidence of individual TEAEs was higher in the CD regimen as compared with ID (Table The majority of patients (97.7%) experienced at least 1 treatment‐related TEAE. The most common treatment‐related TEAEs were hyperphosphatemia (overall, 81.8%; ID, 80.6%; CD, 84.6%), dysgeusia (overall, 40.9%; ID, 32.3%; CD, 61.5%), stomatitis (overall, 40.9%; ID, 25.8%; CD, 76.9%), alopecia (overall, 38.6%; ID, 32.3%; CD, 53.8%), and nausea (overall, 31.8%; ID, 32.3%; CD, 30.8%) (Table Overall, 22 patients (50%; 12 [38.7%] in ID and 10 [76.9%] in CD) had a TEAE leading to dose interruption. Six patients (13.6%; 5 [16.1%] in ID and 1 [7.7%] in CD) had a TEAE leading to dose reduction. Four patients (9.1%; all in ID [12.9%]) had a TEAE leading to pemigatinib discontinuation. The most common TEAE leading to dose interruption was hyperphosphatemia (15.9%; ID, 9.7%; CD, 30.8%). No patients discontinued pemigatinib treatment due to hyperphosphatemia. The most common TEAE leading to dose reduction was fatigue (overall, 4.5%; ID, 6.5%; CD, 0%). All TEAEs leading to dose reduction were considered related to pemigatinib, except for 1 Grade 2 event of fatigue. All TEAEs leading to treatment discontinuation occurred with ID (13.5 mg QD) and included ascites, metastatic brain cancer, malignant neoplasm progression, and hyperesthesia in one patient (2.3%) each. Of these, only hyperesthesia (Grade 1) was considered related to pemigatinib.Serious TEAEs occurred in 16 patients (14 [45.2%] in ID and 2 [15.4%] in CD). Three (6.8%) of these patients had a TEAE with a fatal outcome: malignant neoplasm progression in two patients and dyspnea in one patient. Each of these events were considered unrelated to pemigatinib. All three patients had discontinued treatment attributable to progressive disease. Cholangitis, decreased appetite, and malignant neoplasm progression (in two patients each) were the only serious TEAEs reported in more than one patient.Clinically notable TEAEs occurred in 88.6% of patients (ID, 90.3%; CD, 84.6%) (Table Hyperphosphatemia or “blood phosphorous increased” was reported in 37 (84.1%) patients (26 patients in the ID and 11 in the CD regimen). None of the events were Grade ≥3. Hyperphosphatemia led to dose interruption in 7 (15.9%) patients and dose reduction in 1 (2.3%) patient. Hypophosphatemia was reported in 2 (4.5%) patients, 1 each in 13.5 mg ID and 13.5 mg CD regimens. Both events were Grade 2 in severity. The hypophosphatemia event in the ID regimen was considered treatment‐related. None of the hypophosphatemia events led to pemigatinib dose interruption or reduction. Notably, half of patients in the study received lanthanum carbonate, a phosphate‐binding agent for the treatment of hyperphosphatemia (including prophylaxis).Clinically notable ocular TEAEs included dry eye in 11 (25%) patients (comprised of dry eye: 3 [6.8%]), keratitis: 5 [11.4%], punctate keratitis: 3 [6.8%], and lacrimation increased: 1 [2.3%] as well as serous retinal detachment in 8 (18.2%) patients (including serous retinal detachment: 5 [11.4%], subretinal fluid: 2 [4.5%], and chorioretinopathy: 1 [2.3%]; Table 