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THE CLINICAL RESPONSE RATES OF PEMAZYRE™ (PEMIGATINIB)

PEMAZYRE was studied in the FIGHT-202 trial1

FIGHT-202 was a multicenter, open-label, single-arm study in previously treated patients with locally advanced unresectable or metastatic cholangiocarcinoma.

  • The efficacy population consists of 107 patients with disease that had progressed on or after at least 1 prior therapy and who had an FGFR2 fusion or rearrangement, as determined by clinical trial assay performed in a central laboratory
  • Patients received PEMAZYRE in 21-day cycles at a dosage of 13.5 mg orally once daily for 14 days, followed by 7 days off therapy 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 independent review committee (IRC) according to RECIST v1.1
  • All patients had received at least 1 prior line of systemic therapy, with some having 3 or more prior lines of therapy

PEMAZYRE demonstrated a 36% ORR1

Chart showing ORR: the primary endpoint

Median time to response was 2.7 months (range, 0.7-6.9 months)

Median DoR with
PEMAZYRE was
9.1 months1,*

Patients with DoR:

  • ≥6 months: 63% (n=24)
  • ≥12 months: 18% (n=7)

CI=confidence interval; CR=complete response; PR=partial response; RECIST, Response Evaluation Criteria in Solid Tumors.

95% CI was 6.0-14.5 months and was calculated using the Brookmeyer and Crowley's method.1

THE SAFETY PROFILE OF PEMAZYRE1

The safety of PEMAZYRE was evaluated in FIGHT-202, which included 146 patients with previously treated, locally advanced or metastatic cholangiocarcinoma. 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).

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.

Adverse reactions leading to permanent discontinuation occurred in 9% of patients1

Adverse reactions requiring permanent discontinuation in ≥1% of patients included intestinal obstruction and acute kidney injury.

Select laboratory abnormalities (≥10%) worsening from baseline in patients receiving PEMAZYRE in FIGHT-202

PEMAZYREa
N=146
Laboratory Abnormality
All Gradesb
(%)
Grades ≥3
(%)
Hematology
Decreased hemoglobin
43
6
Decreased lymphocytes
36
8
Decreased platelets
28
3.4
Increased leukocytes
27
0.7
Decreased leukocytes
18
1.4
Chemistry
Increased phosphatec
94
0
Decreased phosphate
68
38
Increased alanine aminotransferase
43
4.1
Increased aspartate aminotransferase
43
6
Increased 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
10
Increased bilirubin
26
6
Decreased potassium
26
5
Decreased 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.

bGraded per NCI CTCAE 4.03.

cBased on CTCAE 5.0 grading.

dGraded based on comparison to upper limit of normal.

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.

Adverse reactions (≥15%) in patients receiving PEMAZYRE in FIGHT-202

 
PEMAZYRE
N=146
Adverse Reaction
All Gradesa
(%)
Grades ≥3*
(%)
Metabolism and nutrition disorders
Hyperphosphatemiab
60
0
Decreased appetite
33
1.4
Hypophosphatemiac
23
12
Dehydration
15
3.4
Skin and subcutaneous tissue disorders
Alopecia
49
0
Nail toxicityd
43
2.1
Dry skin
20
0.7
Palmar-plantar erythrodysesthesia syndrome
15
4.1
Gastrointestinal disorders
Diarrhea
47
2.7
Nausea
40
2.1
Constipation
35
0.7
Stomatitis
35
5
Dry mouth
34
0
Vomiting
27
1.4
Abdominal pain
23
4.8
General disorders
Fatigue
42
4.8
Edema peripheral
18
0.7
Nervous system disorders
Dysgeusia
40
0
Headache
16
0
Eye disorders
Dry eyee
35
0.7
Musculoskeletal and connective tissue disorders
Arthralgia
25
6
Back pain
20
2.7
Pain in extremity
19
2.1
Infections and infestations
Urinary tract infection
16
2.7
Investigations
Weight loss
16
2.1

*Only Grades 3 – 4 were identified.

aGraded per NCI CTCAE 4.03.

bIncludes 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.

Retinal pigment epithelial detachment (RPED)1

  • PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia
  • Of 466 patients who received PEMAZYRE across clinical trials, RPED occurred in 6%, including Grade 3-4 RPED in 0.6%
    • RPED led to dose interruption of PEMAZYRE in 1.7% of patients, and dose reduction and permanent discontinuation in 0.4% and in 0.4% of patients, respectively
    • RPED resolved or improved to Grade 1 levels in 87.5% of patients who required dosage modification of PEMAZYRE for RPED

Recommendations for identification of 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.

Hyperphosphatemia1

  • Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE
  • Of 466 patients who received PEMAZYRE across clinical trials, hyperphosphatemia was reported in 92% 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 29% of patients receiving PEMAZYRE

Recommendations for management of hyperphosphatemia

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 as recommended in the Prescribing Information.

Embryo-fetal toxicity1

  • Based on findings in an animal study and its mechanism of action and findings in an animal reproduction study, PEMAZYRE 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 patients of potential risks

Pregnant women

Advise pregnant women of the potential risk to the fetus.


Female patients

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 patients not to breastfeed during treatment with PEMAZYRE and for 1 week after the final dose.

Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the final dose.


Male patients

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for at least 1 week after the final dose of PEMAZYRE.

Testing and selecting patients for PEMAZYRE

Molecular profiling is necessary to detect FGFR2 fusions or rearrangements

Test for FGFR2 fusions using an FDA-approved companion diagnostic test that meets the following criteria for detection2-5:

  • Specifically detects FGFR2 fusions (distinct from FGFR2 mutations)
  • Detects FGFR2 fusions with a wide range of fusion partners (whether known or unknown)

Patient selection for PEMAZYRE1

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.

Information on FDA-approved test(s) for the detection of an FGFR2 fusion or rearrangement in cholangiocarcinoma is available at
http://www.fda.gov/CompanionDiagnostics.

RECOMMENDED DOSING AND SCHEDULE OF PEMAZYRE

Dosing with PEMAZYRE1

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

Graphic showing 14 days of once-daily therapy and 7 days of no therapy

Continue treatment until disease progression or unacceptable toxicity occurs1

How to take PEMAZYRE1

  • PEMAZYRE can be taken with or without food at approximately the same time every day
  • Instruct patients to take their dose of PEMAZYRE at approximately the same time every day
  • Swallow tablets whole. Do not crush, chew, split, or dissolve tablets
  • If the patient misses a dose by 4 or more hours or if vomiting occurs, resume dosing with the next scheduled dose

Dose modifications1

  • PEMAZYRE is available in 3 strengths to enable dose modifications as needed—First dose reduction from 13.5 mg to 9 mg once daily; second dose reduction from 9 mg to 4.5 mg once daily
  • Dose modifications may be required for adverse reactions including RPED, hyperphosphatemia and other adverse reactions ≥ Grade 3
  • Avoid concomitant use of strong and moderate CYP3A inducers during treatment with PEMAZYRE
  • If concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided, reduce PEMAZYRE dose

PEMAZYRE is dispensed by Biologics by McKesson specialty pharmacy. To request PEMAZYRE
for your patient, please call 800.850.4306 or complete and fax a PEMAZYRE Enrollment Form.

IMPORTANT SAFETY INFORMATION

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 466 patients who received PEMAZYRE across clinical trials, RPED occurred in 6% of patients, including Grade 3-4 RPED in 0.6%. The median time to first onset of RPED was 62 days. RPED led to dose interruption of PEMAZYRE in 1.7% of patients, and dose reduction and permanent discontinuation in 0.4% and in 0.4% of patients, respectively. RPED resolved or improved to Grade 1 levels in 87.5% 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 in the prescribing information for PEMAZYRE.

Dry eye: Among 466 patients who received PEMAZYRE across clinical trials, dry eye occurred in 27% of patients, including Grade 3-4 in 0.6% of patients. Treat patients with ocular demulcents as needed.

Hyperphosphatemia
Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE. Among 466 patients who received PEMAZYRE across clinical trials, hyperphosphatemia was reported in 92% 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 29% 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 as recommended in the prescribing information.

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 final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the final dose.

Adverse Reactions
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, arthalgia, 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.

Clinically relevant adverse reactions occurring in ≤ 10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 1.3% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N=466]).

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.

The most common adverse reactions (incidence ≥20%) were hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry skin.

Drug Interactions
Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce the dose of PEMAZYRE if concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.

Special Populations
Advise lactating women not to breastfeed during treatment with PEMAZYRE and for 1 week after the final dose.

References: 1. PEMAZYRE Prescribing Information. Incyte Corporation. 2. Lowery MA, Ptashkin R, Jordan E, et al. Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res. 2018;24(17):4154-4161. 3. Javle MM, Murugesan K, Shroff RT, et al. Profiling of 3,634 cholangiocarcinomas (CCA) to identify genomic alterations (GA), tumor mutational burden (TMB), and genomic loss of heterozygosity (gLOH). J Clin Oncol. 2019;37(15 suppl):4087. 4. Hollebecque A, de Bono JS, Plummer R, et al. 7OPhase I study of CC-90011 in patients with advanced solid tumors and relapsed/refractory non-Hodgkin lymphoma (R/R NHL). Ann Oncol. 2019;30(suppl 1):mdz029. 5. Frampton GM, Fichtenholtz A, Otto GA, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013;31(11):1023-1031.

Please see Full Prescribing Information for PEMAZYRE.

INDICATIONS AND USAGE

PEMAZYRE is a kinase inhibitor 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).