Pemigatinib
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alara Ece Dagsali, M.D.
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Overview
Pemigatinib is a inhibits FGFR kinase activity that is FDA approved for the treatment of Cholangiocarcinoma PEMAZYRE is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement PEMAZYRE is indicated for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement.. Common adverse reactions include The following adverse reactions are discussed elsewhere in the labeling:
- Ocular Toxicity
- Hyperphosphatemia and Soft Tissue Mineralization.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Cholangiocarcinoma PEMAZYRE is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement PEMAZYRE is indicated for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement.
DOSAGE Cholangiocarcinoma
The recommended dosage of PEMAZYRE is 13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy, in 21-day cycles. Continue treatment until disease progression or unacceptable toxicity occurs.
Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement
The recommended dosage of PEMAZYRE is 13.5 mg orally once daily on a continuous basis. Continue treatment until disease progression or unacceptable toxicity occurs.
Tablets:
- 4.5 mg: round, white to off-white tablet debossed on one side with "I" and "4.5" on the other side.
- 9 mg: oval, white to off-white tablet debossed on one side with "I" and "9" on the other side.
- 13.5 mg: round, white to off-white tablet debossed on one side with "I" and "13.5" on the other side.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pemigatinib in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pemigatinib in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Pemigatinib FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pemigatinib in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pemigatinib in pediatric patients.
Contraindications
None.
Warnings
Ocular Toxicity Retinal Pigment Epithelial Detachment (RPED)
PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is unknown.
Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED.
Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment. For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE.
Modify the dose or permanently discontinue PEMAZYRE as recommended.
Dry Eye
Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients. Treat patients with ocular demulcents as needed.
Hyperphosphatemia and Soft Tissue Mineralization PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYR. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE.
Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is > 5.5 mg/dL. For serum phosphate levels > 7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia [see Dosage and Administration (2.3)].
Embryo-Fetal Toxicity Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm when administered to a pregnant woman. Oral administration of pemigatinib to pregnant rats during the period of organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 13.5 mg.
Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose .
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the WARNINGS AND PRECAUTIONS section reflects exposure to PEMAZYRE at a starting dose of 13.5 mg orally once daily (intermittent or continuous administration) in 635 patients with advanced malignancies. Among the 635 patients, 31% were exposed for 6 months or longer and 11% were exposed greater than one year, including patients with previously treated, advanced, or metastatic cholangiocarcinoma in FIGHT-202 and patients with MLNs with FGFR1 rearrangement in FIGHT-203.
Cholangiocarcinoma
FIGHT-202
The safety of PEMAZYRE was evaluated in FIGHT-202, which included 146 patients with previously treated, locally advanced or metastatic cholangiocarcinoma [see Clinical Studies (14.1)]. Patients were treated orally with PEMAZYRE 13.5 mg once daily for 14 days on followed by 7 days off therapy until disease progression or unacceptable toxicity. The median duration of treatment was 181 days (range: 7 to 730 days).
The median age of PEMAZYRE-treated patients was 59 years (range 26-78), 58% were females, and 71% were White.
Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE. Serious adverse reactions in ≥ 2% of patients who received PEMAZYRE included abdominal pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract infection. Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion.
Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥ 1% of patients included intestinal obstruction and acute kidney injury.
Dosage interruptions due to an adverse reaction occurred in 43% of patients who received PEMAZYRE. Adverse reactions requiring dosage interruption in ≥ 1% of patients included stomatitis, palmar-plantar erythrodysesthesia syndrome, arthralgia, fatigue, abdominal pain, AST increased, asthenia, pyrexia, ALT increased, cholangitis, small intestinal obstruction, alkaline phosphatase increased, diarrhea, hyperbilirubinemia, electrocardiogram QT prolonged, decreased appetite, dehydration, hypercalcemia, hyperphosphatemia, hypophosphatemia, back pain, pain in extremity, syncope, acute kidney injury, onychomadesis, and hypotension.
Dose reductions due to an adverse reaction occurred in 14% of patients who received PEMAZYRE. Adverse reactions requiring dosage reductions in ≥ 1% of patients who received PEMAZYRE included stomatitis, arthralgia, palmar-plantar erythrodysesthesia syndrome, asthenia, and onychomadesis.
Increased Creatinine
Within the first 21-day cycle of PEMAZYRE dosing, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed [see Clinical Pharmacology (12.3)].
Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement
FIGHT-203
The safety of PEMAZYRE was evaluated in FIGHT-203, which included 34 patients who were treated for MLN with FGFR1 rearrangement [see Clinical Studies (14.2)]. Patients were treated with PEMAZYRE 13.5 mg once daily on a continuous schedule (the approved recommended starting dosage) or for 14 days on followed by 7 days off therapy (an unapproved dosage regimen in MLN with FGFR1 rearrangement) until disease progression, unacceptable toxicity, or they were able to receive allogeneic stem cell transplant. The median duration of treatment was 205 days (range: 30-1347 days).
Serious adverse reactions occurred in 53% of patients receiving PEMAZYRE at all dosages. Serious adverse reactions in > 5% of patients included acute kidney injury. Fatal adverse reactions occurred in 9% of patients who received PEMAZYRE, including acute kidney injury, multiple organ dysfunction syndrome, and malignant neoplasm progression, occurring in one patient each.
Permanent discontinuation due to an adverse reaction occurred in 12% of patients who received PEMAZYRE at all dosages. Adverse reactions requiring permanent discontinuation included cardiac failure, multiple organ dysfunction syndrome, blood alkaline phosphatase increase, and calciphylaxis.
In patients who started treatment on the recommended dosage (n = 20), adverse reactions requiring dosage interruption of PEMAZYRE occurred in 80% of patients. Adverse reactions which required dosage interruption in > 2 patients treated at the recommended dosage included nail toxicities (20%) and hyperphosphatemia (15%).
Dose reductions of PEMAZYRE due to an adverse reaction occurred in 80% of patients who started treatment on the recommended dosage. Adverse reactions requiring dose reductions occurring in > 2 patients were nail toxicities (20%), hyperphosphatemia (20%), and alopecia (15%).
The most common (≥ 20%) adverse reactions were hyperphosphatemia, nail toxicity, alopecia, stomatitis, diarrhea, dry eye, fatigue, rash, abdominal pain, anemia, constipation, dry mouth, epistaxis, serous retinal detachment, extremity pain, decreased appetite, dry skin, dyspepsia, back pain, nausea, blurred vision, peripheral edema, and dizziness.
The most common (≥ 20%) laboratory abnormalities were increased phosphate, decreased lymphocytes, decreased leukocytes, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased aspartate aminotransferase, decreased neutrophils, increased creatinine, decreased phosphate, decreased sodium, increased glucose, decreased platelets, decreased calcium, increased calcium, decreased potassium, and increased bilirubin.
Postmarketing Experience
There is limited information regarding Pemigatinib Postmarketing Experience in the drug label.
Drug Interactions
Effect of Other Drugs on PEMAZYRE Strong and Moderate CYP3A Inducers
Concomitant use of PEMAZYRE with a strong or moderate CYP3A inducer decreases pemigatinib plasma concentrations, which may reduce the efficacy of PEMAZYRE. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.
Strong and Moderate CYP3A Inhibitors
Concomitant use of a strong or moderate CYP3A inhibitor with PEMAZYRE increases pemigatinib plasma concentrations, which may increase the incidence and severity of adverse reactions. Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce PEMAZYRE dosage if concomitant use of strong and moderate CYP3A inhibitors cannot be avoided
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Pemigatinib in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Pemigatinib in women who are pregnant.
Labor and Delivery
Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm or loss of pregnancy when administered to a pregnant woman. There are no available data on the use of PEMAZYRE in pregnant women. Oral administration of pemigatinib to pregnant rats during the period of organogenesis at maternal plasma exposures below the human exposure at the clinical dose of 13.5 mg resulted in fetal malformations, fetal growth retardation, and embryo-fetal death. Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectivel
Nursing Mothers
There are no data on the presence of pemigatinib or its metabolites in human milk or their effects on either the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children from PEMAZYRE, advise women not to breastfeed during treatment and for 1 week after the last dose.
Pediatric Use
In 4- or 13-week repeat-dose toxicology studies in rats and non-human primates, animals displayed toxicities in bone and teeth at pemigatinib exposures lower than the human exposure at the clinical dose of 13.5 mg. Physeal and cartilage dysplasia were present in multiple bones in both species, and tooth (incisor) abnormalities (complete loss of ameloblasts with associated secondary changes) occurred in rats. Six weeks after cessation of dosing, these findings did not show complete evidence of recovery, and additional tooth-related findings (mal-aligned, whitened, broken, and trimmed/thinned incisors) developed in the 13-week study.
Geriatic Use
In FIGHT-202 in patients with cholangiocarcinoma, 32% of patients were 65 years and older, and 8% of patients were 75 years and older. In FIGHT-203 in patients with MLN with FGFR1 rearrangement, 44% of patients were 65 years and older, and 2.9% of patients were 75 years and older.
No overall differences in safety or effectiveness were observed between these patients and younger patients.
Gender
PEMAZYRE can cause fetal harm when administered to pregnant women.
Pregnancy Testing
Verify pregnancy status of females of reproductive potential prior to initiating PEMAZYRE.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose.
Males
Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose.
Race
There is no FDA guidance on the use of Pemigatinib with respect to specific racial populations.
Renal Impairment
Reduce the recommended dosage of PEMAZYRE for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2, estimated by MDRD equation).
No dosage adjustment is recommended for patients with mild or moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m2). No dosage adjustment is recommended for patients with end-stage renal disease (eGFR < 15 mL/min/1.73 m2) who are receiving intermittent hemodialysis.
Hepatic Impairment
Reduce the recommended dosage of PEMAZYRE for patients with severe hepatic impairment (total bilirubin > 3 × ULN with any AST).
No dosage adjustment is recommended for patients with mild (total bilirubin > upper limit of normal [ULN] to 1.5 × ULN or AST > ULN) or moderate (total bilirubin >1.5–3 × ULN with any AST) hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Pemigatinib in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Pemigatinib in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Pemigatinib Administration in the drug label.
Monitoring
Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is > 5.5 mg/dL. For serum phosphate levels > 7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia
IV Compatibility
There is limited information regarding the compatibility of Pemigatinib and IV administrations.
Overdosage
There is limited information regarding Pemigatinib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Pemigatinib Pharmacology in the drug label.
Mechanism of Action
Pemigatinib is a small molecule kinase inhibitor that targets FGFR1, 2 and 3 with IC50 values of less than 2 nM. Pemigatinib also inhibited FGFR4 in vitro at a concentration approximately 100 times higher than those that inhibit FGFR1, 2, and 3. Pemigatinib inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines with activating FGFR amplifications and fusions that resulted in constitutive activation of FGFR signaling. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Pemigatinib exhibited anti-tumor activity in mouse xenograft models of human tumors with FGFR1, FGFR2, or FGFR3 alterations resulting in constitutive FGFR activation including a patient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic FGFR2-Transformer-2 beta homolog (TRA2b) fusion protein and the KG1 leukemia model that carries a translocation of FGFR1 (FGFR1OP2-FGFR1).
Structure
There is limited information regarding Pemigatinib Structure in the drug label.
Pharmacodynamics
Serum Phosphate
Pemigatinib increased serum phosphate levels as a consequence of FGFR inhibition. Serum phosphate increased with increasing exposure across the dose range of 1 to 20 mg once daily (0.07 to 1.5 times the recommended dose), with increased risk of hyperphosphatemia with higher pemigatinib exposure.
Cardiac Electrophysiology
At a dose 1.5 times the maximum recommended dose, PEMAZYRE does not result in a large mean increase (i.e. > 20 ms) of the QTc interval.
Pharmacokinetics
The geometric mean (CV%) steady-state pemigatinib AUC0-24h was 2620 nM·h (54%) and Cmax was 236 nM (56%) for 13.5 mg orally once daily. Steady state pemigatinib concentrations increased proportionally over the dose range of 1 to 20 mg (0.07 to 1.5 times the recommended dose). Steady-state was achieved within 4 days and pemigatinib accumulated with a median accumulation ratio of 1.63 (range 0.63 to 3.28) following repeated once daily dosing.
Absorption
The median time to achieve peak pemigatinib plasma concentration (Tmax) was 1.13 (0.50‑6.00) hours.
Effect of Food
Administration of PEMAZYRE with a high-fat and high-calorie meal (approximately 1000 calories with 150 calories from protein, 250 calories from carbohydrate, and 500‑600 calories from fat) had no clinically significant effect on pemigatinib pharmacokinetics.
Distribution
The estimated apparent volume of distribution was 235 L (60.8%) following a 13.5 mg oral dose. Protein binding of pemigatinib was 90.6% and was independent of concentration in vitro.
Elimination
The geometric mean (%CV) elimination half-life (t½) of pemigatinib was 15.4 (51.6%) hours and the geometric mean apparent clearance (CL/F) was 10.6 L/h (54%).
Metabolism
Pemigatinib is predominantly metabolized by CYP3A4 in vitro. The major drug-related moiety in plasma was unchanged pemigatinib.
Excretion
Following a single oral 11 mg dose of radiolabeled pemigatinib, 82.4% of the dose was recovered in feces (1.4% as unchanged) and 12.6% in urine (1% as unchanged).
Specific Populations
No clinically significant differences in the systemic exposure of pemigatinib were observed based on age (21 ‑ 79 years), sex, race/ethnicity (White 68.2%, Asian 16%, Black 6.3%, Hispanic 6%, other 3.5%) or body weight (39.8 ‑ 156 kg).
Patients with Renal Impairment
No clinically significant differences in the systemic exposure of pemigatinib were observed in mild to moderate renal impairment (eGFR 30 to 89 mL/min, MDRD) or end-stage renal disease (eGFR <15 mL/min/1.73 m2) on intermittent hemodialysis. Compared to subjects with normal renal function, the geometric mean pemigatinib AUC0–inf increased by 59% in patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2).
Patients with Hepatic Impairment
No clinically significant differences in the systemic exposure of pemigatinib were observed in mild (total bilirubin > upper limit of normal [ULN] to 1.5 × ULN or AST > ULN) to moderate (total bilirubin >1.5–3 × ULN with any AST) hepatic impairment. Compared to subjects with normal hepatic function, the geometric mean pemigatinib AUC0–inf increased by 136% in subjects with severe hepatic impairment (total bilirubin > 3 × ULN with any AST).
Drug Interaction Studies
Clinical Studies and Model-Based Approaches
CYP3A Inhibitors: Itraconazole (strong CYP3A inhibitor) increased Cmax by 17% and increased AUC by 88% following a single oral PEMAZYRE dose of 4.5 mg [see Drug Interactions (7.1)]. Concomitant use of moderate CYP3A inhibitors is predicted to increase pemigatinib exposure by approximately 50-80%.
CYP3A Inducers: Rifampin (strong CYP3A inducer) decreased pemigatinib Cmax by 62% and AUC by 85% following a single oral PEMAZYRE dose of 13.5 mg. Concomitant use of a moderate CYP3A inducer is predicted to decrease pemigatinib exposure by more than 50%.
Other Drugs: No clinically significant differences in pemigatinib exposure when co-administered with esomeprazole (proton pump inhibitor) or ranitidine (histamine-2 antagonist). No clinically significant differences in glucose levels were observed when metformin (OCT2/MATE1 substrate) was co-administered with pemigatinib.
In Vitro Studies
CYP Enzymes: Pemigatinib is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 or an inducer of CYP1A2, CYP2B6, or CYP3A4.
Transporter Systems: Pemigatinib is a substrate of both P-gp and BCRP. P-gp or BCRP inhibitors are not expected to affect pemigatinib exposure at clinically relevant concentrations. Pemigatinib is an inhibitor of P-gp, OCT2, and MATE1. Pemigatinib may increase serum creatinine by decreasing renal tubular secretion of creatinine; this may occur due to inhibition of renal transporters OCT2 and MATE1 and may not affect glomerular function
Nonclinical Toxicology
Carcinogenicity studies have not been conducted with pemigatinib.
Pemigatinib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay and was not clastogenic in either an in vitro chromosome aberration assay or an in vivo micronucleus assay in rats.
Dedicated fertility studies with pemigatinib have not been conducted. Oral administration of pemigatinib did not result in any dose-related findings likely to result in impaired fertility in male and female reproductive organs.
Clinical Studies
Cholangiocarcinoma FIGHT-202 (NCT02924376), a multicenter open-label single-arm trial, evaluated the efficacy of PEMAZYRE in 107 patients with locally advanced unresectable or metastatic cholangiocarcinoma whose disease had progressed on or after at least 1 prior therapy and who had an FGFR2 gene fusion or non-fusion rearrangement, as determined by a clinical trial assay performed at a central laboratory. Qualifying in-frame fusions and other rearrangements were predicted to have a breakpoint within intron 17/exon 18 of the FGFR2 gene leaving the FGFR2 kinase domain intact.
Patients received PEMAZYRE in 21-day cycles at a dosage of 13.5 mg orally once daily for 14 consecutive days, followed by 7 days off therapy. PEMAZYRE was administered until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DoR) as determined by an independent review committee (IRC) according to RECIST v1.1.
The median age was 56 years (range: 26 to 77 years), 61% were female, 74% were White, and 95% had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 (42%) or 1 (53%). Ninety-eight percent of patients had intrahepatic cholangiocarcinoma. Eighty-six percent of patients had in-frame FGFR2 gene fusions and the most commonly identified FGFR2 fusion was FGFR2-BICC1 (34%). Fourteen percent of patients had other FGFR2 rearrangements that could not be confidently predicted to be in-frame fusions, including rearrangements without an identifiable partner gene. All patients had received at least 1 prior line of systemic therapy, 27% had 2 prior lines of therapy, and 12% had 3 or more prior lines of therapy. Ninety-six percent of patients had received prior platinum-based therapy including 76% with prior gemcitabine/cisplatin.
Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement
FIGHT-203 (NCT03011372), a multicenter open-label, single-arm trial, evaluated the efficacy of PEMAZYRE in 28 patients with MLNs with FGFR1 rearrangement. Inclusion criteria included documented myeloid/lymphoid neoplasms with 8p11 rearrangement shown to be an FGFR1 activating mutation, based on cytogenetic evaluation. Patients could have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or after a disease modifying therapy, or were not a candidate for allo-HSCT or other disease modifying therapies.
Patients received PEMAYZRE 13.5 mg once daily in 21-day cycles, either on a continuous schedule (the approved recommended starting dosage) or as an intermittent schedule (14 days on, 7 days off, an unapproved dosage regimen in MLN with FGFR1 rearrangement). PEMAZYRE was administered until disease progression or unacceptable toxicity or until patients were able to receive allo-HSCT. The median age was 65 years (range: 39-78), 64% were female, 68% were White, 3.6% were Black or African American, 11% were Asian, 3.6% were American Indian/Alaska Native, 3.6% were other race, and race was unknown or not collected for 11% of patients; 3.6% were Hispanic, 68% were not Hispanic, 11% were other ethnicity, and ethnicity was not reported in 18%, and 88% had an ECOG performance status of 0 or 1.
In patients with chronic phase in the marrow with or without extramedullary disease (EMD) (N = 18), efficacy was established based on complete response (CR). CR was defined based on the MDS/MPN Working Group response criteria (2015) for MDS/MPN neoplasms with the additional requirement that peripheral eosinophils are < 0.5 × 109/L, and, if relevant, CR in EMD using Lugano criteria (Cheson 2014). The CR rate was 78% (14/18; 95% CI: 52, 94). The median time to response of CR was 104 days (range, 44 to 435 days). The median duration of CR was not reached (range, 1+ to 988+ days).
In patients with blast phase in the marrow with or without EMD (N = 4), efficacy was established based on CR. CR was defined as < 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets > 100,000/microliter and absolute neutrophil counts > 1,000/microliter). Of the 4 patients with blast phase, two patients achieved a CR (duration: 1+ and 94 days).
In patients with EMD only (N = 3), efficacy was established based on CR using Lugano criteria (Cheson 2014). In the 3 patients with EMD only, 1 patient achieved a CR (duration: 64+ days).
For all patients (N = 28 including 3 patients without evidence of morphologic disease), the complete cytogenetic response rate was 79% (22/28; 95% CI: 59, 92).
How Supplied
PEMAZYRE tablets are available as follows:
- 4.5 mg: Round, white to off-white debossed on one side with “I” and “4.5” on the other side in bottles of 14 with child-resistant closure, NDC 50881-026-01
- 9 mg: Oval, white to off-white debossed on one side with “I” and “9” on the other side in bottles of 14 with child-resistant closure, NDC 50881-027-01
- 13.5 mg: Round, white to off-white debossed on one side with “I” and “13.5” on the other side in bottles of 14 with child-resistant closure, NDC 50881-028-01
Storage
Store PEMAZYRE tablets at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Ocular Toxicity
Advise patients that PEMAZYRE may cause ocular toxicity including RPED and to immediately inform their healthcare provider if they experience any visual changes. Also advise patients that they should use artificial tear or substitutes, hydrating or lubricating eye gels in order to prevent or treat dry eyes .
Hyperphosphatemia and Soft Tissue Mineralization
Inform patients that they may experience increase in phosphate levels and of the need to monitor serum phosphate levels. Advise patients to immediately inform their healthcare provider of any symptoms related to acute change in phosphate levels such as muscle cramps, numbness, or tingling around the mouth .
Nail Disorders
Advise patients that PEMAZYRE may cause nail disorders.
Embryo-Fetal Toxicity
Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform female patients of the risk to a fetus and potential loss of pregnancy. Advise females of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 1 week after receiving the last dose of PEMAZYRE. Lactation
Advise patients not to breastfeed during treatment with PEMAZYRE and for 1 week after the last dose. Administration
Instruct patients do not crush, chew, split or dissolve tablets. Instruct patients if they miss a dose by 4 or more hours or if they vomit after taking a dose, resume dosing with the next scheduled dose. Extra tablets should not be taken to make up for the missed dose. Drug Interactions
Advise patients to inform their healthcare providers of all concomitant medications, herbal and dietary supplements. Advise patients to avoid grapefruit products during treatment with PEMAZYRE .
Precautions with Alcohol
Alcohol-Pemigatinib interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
PEMAZYRE
Look-Alike Drug Names
There is limited information regarding Pemigatinib Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.