_______________CONTRAINDICATIONS ________________________HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
PEMAZYRE safely and effectively. See full prescribing information for
PEMAZYRE.

None. (4)__________ WARNINGS AND PRECAUTIONS ___________________

Ocular Toxicity: PEMAZYRE can cause retinal pigment epithelial
detachment. Perform ophthalmological examination including opticalcoherence tomography (OCT) prior to initiation of therapy, every 2 months
for the first 6 months of treatment and every 3 months thereafter, andurgently at any time for visual symptoms. (2.3, 5.1)
Hyperphosphatemia and Soft Tissue Mineralization: PEMAZYRE cancause hyperphosphatemia leading to soft tissue mineralization, cutaneous
calcification, calcinosis, and non-uremic calciphylaxis. Monitor for
hyperphosphatemia and withhold, reduce the dose, or permanently
discontinue based on duration and severity of hyperphosphatemia. (2.3,5.2)
Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients ofreproductive potential of the potential risk to the fetus and use effective
contraception. (5.3, 8.1, 8.3)_______________ ADVERSE REACTIONS ________________________PEMAZYRE®(pemigatinib) tablets, for oral use
Initial U.S. Approval: 2020----------------------RECENT MAJOR CHANGES------------Indications and Usage, Myeloid/Lymphoid Neoplasms with FGFR1
Rearrangement (1.2)
8/2022
Dosage and Administration, Recommended Dosage (2.2)
8/2022
Warnings and Precautions, Ocular Toxicity (5.1)
8/2022
Warnings and Precautions, Hyperphosphatemia and Soft Tissue
Mineralization (5.2)
8/2022_____________ INDICATIONS AND USAGE______________________PEMAZYRE is a kinase inhibitor indicated:
for the treatment of adults with previously treated, unresectable locallyadvanced or metastatic cholangiocarcinoma with a fibroblast growth factor
receptor 2 (FGFR2) fusion or other rearrangement as detected by an
FDA-approved test. (1,2.1)
This indication is approved under accelerated approval based on overall
response rate and duration of response. Continued approval for thisindication may be contingent upon verification and description of clinicalbenefit in a confirmatory trial(s). (1,2.1)
For the treatment of adults with relapsed or refractory myeloid/lymphoidneoplasms (MLNs) with FGFR1 rearrangement. (1,2.1)__________ DOSAGE AND ADMINISTRATION___________________

Cholangiocarcinoma: The most common adverse reactions (incidence≥ 20%) are hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue,
dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased
appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, backpain, and dry skin. (6.1)
Myeloid/lymphoid neoplasms with FGFR1 rearrangement: The mostcommon (≥ 20%) adverse reactions are 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. (6.1)

Cholangiocarcinoma:
Confirm the presence of an FGFR2 fusion or rearrangement prior to initiationof treatment with PEMAZYRE. (2.1)
Recommended dosage 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. (2.2)
Myeloid/lymphoid neoplasms with FGFR1 rearrangement:
Recommended dosage is 13.5 mg orally once daily. Continue treatment until
disease progression or unacceptable toxicity. (2.2)
All patients treated with PEMAZYRE:
Swallow tablet whole, with or without food. (2.2)
Severe Renal Impairment: the recommended dosage of PEMAZYRE is 9 mg
with the schedule (intermittent or continuous) designated for the indication.
(2.5, 8.6, 12.3)
Severe Hepatic Impairment: the recommended dosage of PEMAZYRE is
9 mg with the schedule (intermittent or continuous) designated for theindication. (2.6, 8.7, 12.3)_________ DOSAGE FORMS AND STRENGTHS __________________To report SUSPECTED ADVERSE REACTIONS, contact Incyte
Corporation at 1-855-463-3463 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
_______________ DRUG INTERACTIONS ________________________• Strong and Moderate CYP3A Inducers: Avoid concomitant use of
PEMAZYRE. (7.1)• Strong and Moderate CYP3A Inhibitors: Avoid concomitant use. If
concomitant use cannot be avoided, reduce PEMAZYRE dosage. (2.4, 7.1)__________ USE IN SPECIFIC POPULATIONS ___________________
Lactation: Advise not to breastfeed. (8.2)

See 17 for PATIENT COUNSELING INFORMATION and FDAapproved patient labeling
Revised: 8/2022

Tablets: 4.5 mg, 9 mg, and 13.5 mg. (3)FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1Cholangiocarcinoma
1.2 Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
2.2 Recommended Dosage
2.3 Dosage Modification for Adverse Reactions
2.4 Dosage Modification for Concomitant Use with Strong or Moderate
CYP3A Inhibitors
2.5 Recommended Dosage for Severe Renal Impairment
2.6 Recommended Dosage for Severe Hepatic Impairment
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Ocular Toxicity
5.2 Hyperphosphatemia and Soft Tissue Mineralization
5.3 Embryo-Fetal Toxicity
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
7 DRUG INTERACTIONS
7.1 Effect of Other Drugs on PEMAZYRE
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenicity, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Cholangiocarcinoma
14.2 Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are notlisted.

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FULL PRESCRIBING INFORMATION
1

INDICATIONS AND USAGE

1.1

Cholangiocarcinoma

PEMAZYRE is indicated for the treatment of adults with previously treated, unresectable locallyadvanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2)
fusion or other rearrangement as detected by an FDA-approved test [see Dosage andAdministration (2.1)].
This indication is approved under accelerated approval based on overall response rate andduration of response [see Clinical Studies (14.1)]. Continued approval for this indication may becontingent upon verification and description of clinical benefit in a confirmatory trial(s).

1.2

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.

2

DOSAGE AND ADMINISTRATION

2.1

Patient Selection

Select patients for the treatment of locally advanced or metastatic cholangiocarcinoma with
PEMAZYRE based on the presence of an FGFR2 fusion or rearrangement as detected by an
FDA-approved test [see Clinical Studies (14.1)].
Information on FDA-approved test(s) for the detection of an FGFR2 fusion or rearrangement incholangiocarcinoma is available at http://www.fda.gov/CompanionDiagnostics.
Select patients for the treatment of relapsed or refractory myeloid/lymphoid neoplasms with
FGFR1 rearrangement with PEMAZYRE based on the presence of an FGFR1 rearrangement[see Clinical Studies (14.2)]. An FDA-approved test for detection of FGFR1 rearrangement inpatients with relapsed or refractory myeloid/lymphoid neoplasm for selecting patients fortreatment with PEMAZYRE is not available.

2.2

Recommended Dosage

Take PEMAZYRE with or without food at approximately the same time every day [see ClinicalPharmacology (12.3)].
Swallow tablets whole. Do not crush, chew, split, or dissolve tablets.
If the patient misses a dose of PEMAZYRE by 4 or more hours or if vomiting occurs, resume
dosing with the next scheduled dose.

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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.

2.3

Dosage Modification for Adverse Reactions

The recommended dose reductions for adverse reactions are provided in Table 1.
Table 1:

Recommended Dose Reductions for PEMAZYRE for Adverse Reactions
Recommended Dosage
Cholangiocarcinoma with FGFR2
Fusion or Rearrangement

Dose Reduction

MLNs with FGFR1
Rearrangement

First

9 mg once daily for first 14 days ofeach 21-day cycle

9 mg once daily

Second

4.5 mg once daily for first 14 days ofeach 21-day cycle

4.5 mg once daily

Third

Discontinue

4.5 mg once daily for first 14 daysof each 21-day cycle** Permanently discontinue PEMAZYRE if unable to tolerate 4.5 mg once daily for 14 days of each 21-day cycle.

The recommended dosage modifications for adverse reactions are provided in Table 2.
Table 2:

Recommended Dosage Modifications for PEMAZYRE Adverse Reactions

Adverse Reaction
Retinal Pigment Epithelial
Detachment (RPED)[see Warnings andPrecautions (5.1)]

Severity*

PEMAZYRE Dosage Modification
If asymptomatic and stable on serial
examination, continue PEMAZYRE.
If symptomatic or worsening on serial
examination, withhold PEMAZYRE.
If asymptomatic and improved on
subsequent examination, resume
PEMAZYRE at a lower dose.
If symptoms persist or examination
does not improve, consider
permanent discontinuation of
PEMAZYRE, based on clinicalstatus.

RPED

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Adverse Reaction

Severity*

PEMAZYRE Dosage Modification

Hyperphosphatemia[see Warnings andPrecautions (5.2)]

Serum phosphate> 7 mg/dL to≤ 10 mg/dL

Initiate phosphate lowering therapy andmonitor serum phosphate weekly.
Withhold PEMAZYRE if levels are not< 7 mg/dL within 2 weeks of starting
phosphate lowering therapy.
Resume PEMAZYRE at the same dosewhen phosphate levels are < 7 mg/dL for
first occurrence; resume at a lower doselevel for subsequent recurrences.

Serum phosphate> 10 mg/dL

Initiate phosphate lowering therapy andmonitor serum phosphate weekly.
Withhold PEMAZYRE if levels are not≤ 10 mg/dL within 1 week after starting
phosphate lowering therapy.
Resume PEMAZYRE at the next lower
dose level when phosphate levels are< 7 mg/dL.
Permanently discontinue PEMAZYRE forrecurrence of serum phosphate > 10 mg/dL
following 2 dose reductions.

Grade 3

Withhold PEMAZYRE until resolves to
Grade 1 or baseline.
Resume PEMAZYRE at next lower dose if
resolves within 2 weeks.
Permanently discontinue PEMAZYRE if
does not resolve within 2 weeks.
Permanently discontinue PEMAZYRE forrecurrent Grade 3 after 2 dose reductions.

Grade 4

Permanently discontinue PEMAZYRE.

Other Adverse Reactions*Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
version 4.03.

2.4

Dosage Modification for Concomitant Use with Strong or Moderate
CYP3A Inhibitors

Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. If
concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided:•

Reduce PEMAZYRE dosage from 13.5 mg to 9 mg.

•

Reduce PEMAZYRE dosage from 9 mg to 4.5 mg.

If concomitant use of a strong or moderate CYP3A inhibitor is discontinued, increase the
PEMAZYRE dosage (after 3 plasma half-lives of the CYP3A inhibitor) to the dosage that wasused before starting the strong or moderate inhibitor [see Clinical Pharmacology (12.3)].

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2.5

Recommended Dosage for Severe Renal Impairment

The recommended dosage of PEMAZYRE for patients with severe renal impairment (eGFR
estimated by Modification of Diet in Renal Disease [MDRD] 15 mL/min/1.73 m2 to
29 mL/min/1.73 m2) is 9 mg with the schedule (intermittent or continuous) designated for theindication [see Dosage and Administration (2.2), Use in Specific Populations (8.6) and ClinicalPharmacology (12.3)].

2.6

Recommended Dosage for Severe Hepatic Impairment

The recommended dosage of PEMAZYRE for patients with severe hepatic impairment (total
bilirubin > 3 × ULN with any AST) is 9 mg with the schedule (intermittent or continuous)designated for the indication [see Dosage and Administration (2.2),Use in Specific Populations(8.7) and Clinical Pharmacology (12.3)].

3

DOSAGE FORMS AND STRENGTHS

Tablets:
4.5 mg: round, white to off-white tablet debossed on one side with "I" and "4.5" on the otherside.
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.

4

CONTRAINDICATIONS

None.

5

WARNINGS AND PRECAUTIONS

5.1

Ocular Toxicity

Retinal Pigment Epithelial Detachment (RPED)PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visualfloaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring
including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, theincidence 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.

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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 [see Dosage andAdministration (2.3)].
Dry EyeAmong 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 withocular demulcents as needed.

5.2

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 apharmacodynamic effect of PEMAZYRE [see Clinical Pharmacology (12.2)]. 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 andwithhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration andseverity of hyperphosphatemia [see Dosage and Administration (2.3)].

5.3

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, andembryo-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 [see Use inSpecific Populations (8.1, 8.3)].

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6ADVERSE REACTIONS

The following adverse reactions are discussed elsewhere in the labeling:•

Ocular Toxicity [see Warnings and Precautions (5.1)]•

Hyperphosphatemia and Soft Tissue Mineralization [see Warnings and Precautions(5.2)]

6.1

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 trialsof 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 orcontinuous 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 withpreviously 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

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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.
Table 3 summarizes the adverse reactions in FIGHT-202. Table 4 summarizes laboratory
abnormalities in FIGHT-202.
Table 3:Adverse Reactions (≥ 15%) in Patients Receiving PEMAZYRE in
FIGHT-202
PEMAZYRE
N=146
All Gradesa(%)

Grades 3 or 4(%)

Hyperphosphatemiab

600Decreased appetite

33

1.4

Hypophosphatemiac

23

12

Dehydration

15

3.4

Alopecia

49

0Nail toxicityd

43

2.1

Dry skin20

0.7

Palmar-plantar erythrodysesthesia syndrome

15

4.1

Diarrhea47

2.7

Nausea40

2.1

Constipation

35

0.7

Stomatitis

35

5

Dry mouth

34

0

Vomiting

27

1.4

Abdominal pain

23

4.8

Fatigue42

4.8

Edema peripheral

18

0.7

Dysgeusia

400Headache

160Adverse Reaction
Metabolism and nutrition disorders

Skin and subcutaneous tissue disorders

Gastrointestinal disorders

General disorders

Nervous system disorders

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PEMAZYRE
N=146
All Gradesa(%)

Grades 3 or 4
(%)

35

0.7

Arthralgia

25

6Back pain

20

2.7

Pain in extremity

19

2.1

16

2.7

16

2.1

Adverse Reaction
Eye disorders
Dry eyeeMusculoskeletal and connective tissue disorders

Infections and infestations
Urinary tract infection
Investigations
Weight loss

Graded per NCI CTCAE 4.03.
Includes hyperphosphatemia and blood phosphorous increased; graded based on clinical severity and medical
interventions taken according to the "investigations-other, specify" category in NCI CTCAE v4.03.
cIncludes hypophosphatemia and blood phosphorous decreased.
dIncludes nail toxicity, nail disorder, nail discoloration, nail dystrophy, nail hypertrophy, nail ridging, nail infection,
onychalgia, onychoclasis, onycholysis, onychomadesis, onychomycosis, and paronychia.
eIncludes dry eye, keratitis, lacrimation increased, pinguecula, and punctate keratitis.
abClinically relevant adverse reactions occurring in ≤ 10% of patients included fractures (2.1%). In
all patients treated with pemigatinib, 0.5% experienced pathologic fractures (which included
patients with and without cholangiocarcinoma [N=635]). Soft tissue mineralization, including
cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated withhyperphosphatemia were observed with PEMAZYRE treatment.
Table 4:

Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline inPatients Receiving PEMAZYRE in FIGHT-202
PEMAZYREa
N=146

Laboratory Abnormality

All Gradesb (%)

Grades 3 or 4 (%)

Decreased hemoglobin

436Decreased lymphocytes

36

8Decreased platelets

28

3.4

Increased leukocytes

27

0.7

Decreased leukocytes

18

1.4

94

0

Hematology

Chemistry
Increased phosphatec

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PEMAZYREa
N=146
Laboratory Abnormality

All Gradesb (%)

Grades 3 or 4 (%)

Decreased phosphate

68

38

Increased alanine aminotransferase

43

4.1

Increased aspartate aminotransferase

436Increased calcium

43

4.1

Increased alkaline phosphatase

41

11

Increased creatinined

41

1.4

Decreased sodium

39

12

Increased glucose

36

0.7

Decreased albumin

34

0

Increased urate

30

10Increased bilirubin

26

6

Decreased potassium

265Decreased calcium

17

2.7

Increased potassium

12

2.1

Decreased glucose

11

1.4

aThe denominator used to calculate the rate varied from 142-146 based on the number of patients with a baseline

value and at least one post-treatment value.
Graded per NCI CTCAE 4.03.
cBased on CTCAE 5.0 grading.
dGraded based on comparison to upper limit of normal.
b

Increased Creatinine
Within the first 21-day cycle of PEMAZYRE dosing, serum creatinine increased (mean increaseof 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 weretreated for MLN with FGFR1 rearrangement [see Clinical Studies (14.2)]. Patients were treatedwith 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).
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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, andcalciphylaxis.
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 whostarted 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, backpain, 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.
Table 5 summarizes the adverse reactions in FIGHT-203.
Table 5:Adverse Reactions (≥ 15%) in Patients Receiving PEMAZYRE in
FIGHT-203
PEMAZYRE
N=34
All Gradesa(%)

Grade 3 or 4(%)

Hyperphosphatemiab

74

2.9

Decreased appetite

24

6

Nail toxicityc

62

21

Alopecia

59

0

Rash

35

6

Adverse Reaction
Metabolism and nutrition disorders

Skin and subcutaneous tissue disordersd11
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PEMAZYRE
N=34
All Gradesa(%)

Grade 3 or 4
(%)

24

0

18

9

53

15

50

2.9

35

2.9

Constipation

32

2.9

Dry mouth

320

Dyspepsia

240

Nausea

21

0

50

6

26

0

Vision blurred

21

2.9

Trichiasis

18

2.9

Fatiguek

44

9

Edema peripheral

21

0

Pyrexia

18

2.9

35

18

29

0

Pain in extremity

26

12Back pain

24

9

21

0

Adverse Reaction
Dry skine
Palmar-plantar erythrodysaesthesiafGastrointestinal disorders
Stomatitisg
Diarrhea
Abdominal painh

Eye disorders
Dry eyei
Retinal pigment epithelial detachmentjGeneral disorders

Blood and lymphatic system disorders
AnemiaRespiratory, thoracic, and mediastinal disorders
Epistaxis
Musculoskeletal and connective tissue disordersl

Nervous system disorders
Dizziness

Graded per NCI CTCAE 4.03.
Includes hyperphosphatemia and blood phosphorous increased; graded based on clinical severity and medical
interventions taken according to the "investigations-other, specify" category in NCI CTCAE v4.03.
cIncludes ingrowing nail, nail bed inflammation, nail bed tenderness, nail discoloration, nail disorder, naildystrophy, nail growth abnormal, nail infection, nail pigmentation, onychalgia, onychoclasis, onycholysis,
onychomadesis, onychomycosis, and paronychia.
dIncludes dermatitis, dermatitis acneiform, lichen planus, rash, rash macular, and skin exfoliation.
eIncludes dry skin and xerosis.
fIncludes palmar-erythemia, palmer-plantar erythrodysaesthesia, and plantar erythema.
ab12Reference ID: 5036464

Includes aphthous ulcer, cheilitis, lip ulceration, mouth ulceration, pharyngeal inflammation, stomatitis, and tongue
ulceration.
hIncludes abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal rigidity.
iIncludes dry eye, keratitis, lacrimation increased, meibomian gland dysfunction, and punctate keratitisjIncludes detachment of retinal pigment epithelium, maculopathy, retinal detachment, retinal disorder, retinal
thickening, serous retinal detachment, and subretinal fluid.
kIncludes asthenia and fatigue.
lIncludes back pain and spinal pain.
g

Table 6 summarizes laboratory abnormalities in FIGHT-203.
Table 6:

Select Laboratory Abnormalities (≥ 20%) Worsening from Baseline inPatients Receiving PEMAZYRE in FIGHT-203
PEMAZYRE
N=34a
All Gradesb (%)

Grade 3 or 4 (%)

Decreased lymphocytes

65

16

Decreased leukocytes

65

15Decreased hemoglobin

539Decreased neutrophils

45

12

Decreased platelets

29

15

Increased phosphatec

97

2.9

Increased alkaline phosphatase

62

9

Increased alanine aminotransferase

50

12Increased aspartate aminotransferase

479Increased creatinined

440Decreased phosphate

4126

Decreased sodium

41

9Increased glucose

33

3

Decreased calcium

26

2.9

Increased calcium

26

2.9

Decreased potassium

24

2.9

Increased bilirubin

21

0

Laboratory Abnormality
Hematology

Chemistry

a The denominator used to calculate the rate varied from 31 to 34 based on the number of patients with a baseline

value and at least one post-treatment value.

b Graded per NCI CTCAE 4.03.
c Graded per NCI CTCAE 5.0.

d Based on comparison to upper limit of normal.

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Other clinically significant laboratory abnormalities: Prothrombin time/international normalized
ratio was elevated in 16% (Grade 1 or 2 elevation) of patients. Uric acid was elevated in 18% of
patients, including 2.9% with a Grade 3 or 4 elevation.

7

DRUG INTERACTIONS

7.1

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 [see Clinical Pharmacology (12.3)], which may reduce theefficacy 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 [see Clinical Pharmacology (12.3)], which may increase theincidence 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 [see Dosage and Administration (2.4)].

8

USE IN SPECIFIC POPULATIONS

8.1

Pregnancy

Risk Summary
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 [see Clinical Pharmacology(12.1)]. There are no available data on the use of PEMAZYRE in pregnant women. Oraladministration 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 (see Data). Advise pregnant
women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects andmiscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
Once daily oral administration of pemigatinib to pregnant rats during the period of organogenesis
resulted in 100% embryofetal mortality due to post-implantation loss at doses ≥ 0.3 mg/kg(approximately 0.6 times the human exposure based on AUC at the clinical dose of 13.5 mg).
Fetal survival was unaffected at 0.1 mg/kg per day; however, once daily oral administration of
14
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pemigatinib at the 0.1 mg/kg dose level (approximately 0.2 times the human exposure based on
AUC at the clinical dose of 13.5 mg) resulted in reduced mean fetal body weight and an increasein fetal skeletal and visceral malformations, major blood vessel variations, and reduced
ossification.

8.2

Lactation

Risk Summary
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.

8.3

Females and Males of Reproductive Potential

PEMAZYRE can cause fetal harm when administered to pregnant women [see Use in Specific
Populations (8.1)].
Pregnancy Testing
Verify pregnancy status of females of reproductive potential prior to initiating PEMAZYRE[see Use in Specific Populations (8.1)].
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.

8.4

Pediatric Use

The safety and effectiveness of PEMAZYRE have not been established in pediatric patients.
Animal Toxicity Data
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 inboth species, and tooth (incisor) abnormalities (complete loss of ameloblasts with associatedsecondary changes) occurred in rats. Six weeks after cessation of dosing, these findings did notshow complete evidence of recovery, and additional tooth-related findings (mal-aligned,
whitened, broken, and trimmed/thinned incisors) developed in the 13-week study.

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8.5

Geriatric 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 andolder.
No overall differences in safety or effectiveness were observed between these patients andyounger patients.

8.6

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) [see Dosage andAdministration (2.5) and Clinical Pharmacology (12.3)].
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 [see Clinical Pharmacology (12.3)].

8.7

Hepatic Impairment

Reduce the recommended dosage of PEMAZYRE for patients with severe hepatic impairment(total bilirubin > 3 × ULN with any AST) [see Dosage and Administration (2.6) and ClinicalPharmacology (12.3)].
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 [see Clinical Pharmacology (12.3)].

11

DESCRIPTION

Pemigatinib is a kinase inhibitor with the chemical name 3-(2,6-difluoro-3,5-dimethoxyphenyl)1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3',2':5,6]pyrido[4,3d]pyrimidin-2-one. Pemigatinib has a molecular formula of C24H27F2N5O4 and molecular mass of
487.5 g/mole. Pemigatinib has the following chemical structure:
O
F
N

O

O

O

N

F

N
N

N
H

Pemigatinib is a white to off-white solid that is not hygroscopic. The solubility of pemigatinib is
pH dependent with decreasing solubility observed with increasing pH. PEMAZYRE tablets areuncoated and for oral administration. Tablets are available containing 4.5 mg, 9 mg, or 13.5 mg

16
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of pemigatinib active ingredient. The inactive ingredients include magnesium stearate,
microcrystalline cellulose, and sodium starch glycolate.

12

CLINICAL PHARMACOLOGY

12.1

Mechanism of Action

Pemigatinib is a small molecule kinase inhibitor that targets FGFR1, 2 and 3 with IC50 values ofless 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 apatient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic
FGFR2-Transformer-2 beta homolog (TRA2b) fusion protein and the KG1 leukemia model thatcarries a translocation of FGFR1 (FGFR1OP2-FGFR1).

12.2

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.

12.3

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 recommendeddose). Steady-state was achieved within 4 days and pemigatinib accumulated with a medianaccumulation 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.

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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 andthe 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 wasrecovered 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 inmild 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 withsevere 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 inmild (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 withnormal hepatic function, the geometric mean pemigatinib AUC0–inf increased by 136% in
subjects with severe hepatic impairment (total bilirubin > 3 × ULN with any AST).

18
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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 byapproximately 50-80% [see Drug Interactions (7.1)].
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 [see Drug Interactions(7.1)]. Concomitant use of a moderate CYP3A inducer is predicted to decrease pemigatinib
exposure by more than 50% [see Drug Interactions (7.1)].
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 ofrenal transporters OCT2 and MATE1 and may not affect glomerular function [see Adverse
Reactions (6.1)].

13

NONCLINICAL TOXICOLOGY

13.1

Carcinogenesis, Mutagenesis, Impairment of Fertility

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 ofpemigatinib did not result in any dose-related findings likely to result in impaired fertility inmale and female reproductive organs.

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14

CLINICAL STUDIES

14.1

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 werepredicted 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 lineof systemic therapy, 27% had 2 prior lines of therapy, and 12% had 3 or more prior lines oftherapy. Ninety-six percent of patients had received prior platinum-based therapy including 76%
with prior gemcitabine/cisplatin.
Efficacy results are summarized in Table 7.
The median time to response was 2.7 months (range 0.7 – 6.9 months).
Table 7:

Efficacy Results in FIGHT-202

Efficacy Parameter

PEMAZYRE
N = 107

ORR (95% CI)

36% (27, 45)Complete response

2.8%

Partial response

33%

Median DoR (months) (95% CI)a9.1 (6.0, 14.5)

Patients with DoR ≥ 6 months, n (%)

24 (63%)

Patients with DoR ≥ 12 months, n (%)

7 (18%)

a The 95% confidence interval (CI) was calculated using the Brookmeyer and Crowley's method.

Note: Data are from IRC per RECIST v1.1, and complete and partial responses are confirmed.

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14.2

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 continuousschedule (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 toreceive allo-HSCT. The median age was 65 years (range: 39-78), 64% were female, 68% wereWhite, 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 theadditional 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 wasestablished based on CR. CR was defined as < 5% blasts in the bone marrow, no evidence ofdisease, 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 aCR (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), thecomplete cytogenetic response rate was 79% (22/28; 95% CI 59, 92).

16

HOW SUPPLIED/STORAGE AND HANDLINGPEMAZYRE 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 inbottles 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 bottlesof 14 with child-resistant closure, NDC 50881-027-01

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13.5 mg: Round, white to off-white debossed on one side with “I” and “13.5” on the other side inbottles of 14 with child-resistant closure, NDC 50881-028-01
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).

17

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient 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 thatthey should use artificial tear or substitutes, hydrating or lubricating eye gels in order to preventor treat dry eyes [see Warnings and Precautions (5.1)].
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 [see Warnings and Precautions (5.2)].
Nail Disorders
Advise patients that PEMAZYRE may cause nail disorders [see Adverse Reactions (6.1)].
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 [see Warnings
and Precautions (5.3) and Use in Specific Populations (8.1)].

•

Advise females of reproductive potential to use effective contraception during treatment with
PEMAZYRE and for 1 week after the last dose [see Use in Specific Populations (8.3)].

•

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 [see Use in Specific Populations (8.3)].

Lactation•

Advise patients not to breastfeed during treatment with PEMAZYRE and for 1 week after thelast dose [see Use in Specific Populations (8.2)].

Administration•

Instruct patients do not crush, chew, split or dissolve tablets.

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•

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 forthe missed dose [see Dosage and Administration (2.2)].

Drug Interactions
Advise patients to inform their healthcare providers of all concomitant medications, herbal anddietary supplements. Advise patients to avoid grapefruit products during treatment with
PEMAZYRE [see Drug Interactions (7.1)].
Manufactured for:
Incyte Corporation
Wilmington, DE 19803
PEMAZYRE is a registered trademark of Incyte.
U.S. Patent Nos. 9,611,267 and 10,131,667© 2020-2022 Incyte Corporation. All rights reserved.

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PATIENT INFORMATIONPEMAZYRE® (pemah zeer)(pemigatinib) tablets
What is PEMAZYRE?
PEMAZYRE is a prescription medicine that is used to treat adults with:•bile duct cancer (cholangiocarcinoma) that has spread or cannot be removed by surgery:o who have already received a previous treatment, ando whose tumor has a certain type of abnormal FGFR2 gene.

a type of blood cancer called myeloid/lymphoid neoplasms (MLNs):
o when it has come back or did not respond to treatment, ando whose tumor has a certain type of abnormal FGFR1 gene.
Your healthcare provider will test your cancer for certain types of abnormal FGFR1 or FGFR2 genes and make surethat PEMAZYRE is right for you.
It is not known if PEMAZYRE is safe and effective in children.
•

Before you take PEMAZYRE, tell your healthcare provider about all of your medical conditions, including ifyou:•have vision or eye problems•

have kidney problems•

have liver problems•

are pregnant or plan to become pregnant. PEMAZYRE can harm your unborn baby or cause loss of yourpregnancy (miscarriage). You should not become pregnant during treatment with PEMAZYRE.
Females who can become pregnant:o Your healthcare provider should do a pregnancy test before you start treatment with PEMAZYRE.
o You should use an effective method of birth control during treatment and for 1 week after your last dose of
PEMAZYRE. Talk to your healthcare provider about birth control methods that may be right for you.
o Tell your healthcare provider right away if you become pregnant or think that you may be pregnant.
Males with female partners who can become pregnant:o You should use effective birth control when sexually active during treatment with PEMAZYRE and for 1 week
after your last dose of PEMAZYRE.

are breastfeeding or plan to breastfeed. It is not known if PEMAZYRE passes into your breast milk. Do notbreastfeed during treatment and for 1 week after your last dose of PEMAZYRE.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements.
•

How should I take PEMAZYRE?
•

Take PEMAZYRE exactly as your healthcare provider tells you.

•For cholangiocarcinoma, PEMAZYRE is taken in cycles of 21 days. Take PEMAZYRE 1 time each day for 14 days,
followed by 7 days off treatment, to complete a 21-day treatment cycle.

•

For myeloid/lymphoid neoplasms (MLNs), take PEMAZYRE 1 time each day.

•Take PEMAZYRE at about the same time each day.

•Take PEMAZYRE with or without food.

•

Swallow tablets whole. Do not crush, chew, split, or dissolve PEMAZYRE tablets.

•

You should not eat or drink grapefruit products during treatment with PEMAZYRE.

•Your healthcare provider may change your dose of PEMAZYRE, or may temporarily or completely stop treatment if
you get certain side effects.

•

If you miss a dose of PEMAZYRE, you can take the missed dose within 4 hours on the same day. If more than
4 hours have passed, do not make up the dose. Take your regular dose of PEMAZYRE the next day at the usual
time. Do not take more PEMAZYRE than prescribed to make up for the missed dose.

•

If you vomit after taking PEMAZYRE, do not take another PEMAZYRE tablet. Take your regular dose of
PEMAZYRE the next day at the usual time.

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What are the possible side effects of PEMAZYRE?
PEMAZYRE may cause serious side effects, including:•

Eye problems. Certain eye problems are common with PEMAZYRE but can also be serious. Eye problems include
dry eye or inflamed eyes, inflamed cornea (front part of the eye), increased tears, and a disorder of the retina (aninternal part of the eye). You will need to see an eye specialist for a complete eye exam before you begin treatment
with PEMAZYRE, every 2 months for the first 6 months, and then every 3 months during treatment with
PEMAZYRE.
o You should use artificial tears or substitutes, hydrating or lubricating eye gels as needed, to help prevent or
treat dry eyes.
o Tell your healthcare provider right away if you develop any changes in your vision during treatment with
PEMAZYRE including blurred vision, flashes of light, or see black spots. You may need to see an eye specialist
right away.

High phosphate levels in your blood (hyperphosphatemia) and buildup of minerals in different tissues inyour body. Hyperphosphatemia is common with PEMAZYRE but can also be serious. High levels of phosphate inyour blood may lead to buildup of minerals such as calcium, in different tissues in your body. Your healthcare
provider will check your blood phosphate levels during treatment with PEMAZYRE.
o Your healthcare provider may prescribe changes in your diet or phosphate lowering therapy, or change,interrupt or stop PEMAZYRE if needed.
o Tell your healthcare provider right away if you develop any muscle cramps, or numbness or tingling aroundyour mouth.
The most common side effects of PEMAZYRE for cholangiocarcinoma include:••

hair loss• dry eyes•

diarrhea• dry mouth•

nails separate from the bed or poor formation of
the nail• decrease in appetite•

feeling tired•

change in sense of taste• joint pain•

nausea•constipation•

mouth sores• vomiting• stomach-area (abdominal) pain
• low phosphate in blood• back pain
• dry skin

The most common side effects of PEMAZYRE for myeloid/lymphoid neoplasms (MLNs) include:•

nails separate from the bed or poor formation of
the nail• nose bleeds•

hair loss•

mouth sores• pain in feet or hands•

diarrhea•

dry eyes•

tiredness•anemia•stomach-area (abdominal) pain

•

rash

•

constipation•

dry mouth• disorder of the retina• decreased appetite• dry skin
• indigestion• back pain
• nausea• blurry vision• swelling in feet, legs, hands, or arms
• dizziness

These are not all the possible side effects of PEMAZYRE. For more information, ask your healthcare provider or
pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store PEMAZYRE?
• Store PEMAZYRE at room temperature between 68°F to 77°F (20°C to 25°C).
Keep PEMAZYRE and all medicines out of the reach of children.

Reference ID: 5036464

General information about the safe and effective use of PEMAZYRE.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use
PEMAZYRE for a condition for which it is not prescribed. Do not give PEMAZYRE to other people, even if they havethe same symptoms you have. It may harm them. If you would like more information, talk with your healthcare provider.
You can ask your pharmacist or healthcare provider for information that is written for healthcare professionals.
What are the ingredients in PEMAZYRE?
Active ingredient: pemigatinib
Inactive ingredients: magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.
Manufactured for: Incyte Corporation, Wilmington, DE 19803
PEMAZYRE is a registered trademark of Incyte.
© 2020-2022 Incyte Corporation. All rights reserved.
For more information, call Incyte at 1-855-463-3463 or go to www.PEMAZYRE.com
This Patient Information has been approved by the U.S. Food and Drug Administration.

Reference ID: 5036464

Revised: 8/2022