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Turn to PEMAZYRE for Second-Line Treatment

Turn to PEMAZYRE for Second-Line Treatment

PEMAZYRE was studied in the FIGHT-202 study1

FIGHT-202 was a multicenter, open-label, single-arm study in previously treated patients with locally advanced or metastatic cholangiocarcinoma (N=146).

  • The efficacy population consisted of 107 patients with disease that had progressed on or after at least 1 prior therapy and who had an FGFR2 fusion or non-fusion rearrangement, as determined by a clinical trial assay (FoundationOne® CDx) performed at 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 an 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
1+ year
OF CLINICAL EXPERIENCE since FDA approval with 650+ patients treated2,*
*Commercially available in the US since 2020.
Letter i icon

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Recommend pemigatinib (PEMAZYRE) as a subsequent-line treatment option for unresectable or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements following disease progression3,†,‡,§

See the Guidelines online at NCCN.org for the full recommendation.

NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

§Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

 
 
Letter i icon

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Recommend pemigatinib (PEMAZYRE) as a subsequent-line treatment option for unresectable or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements following disease progression3,†,‡,§

See the Guidelines online at NCCN.org for the full recommendation.

NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

§Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

 
36% ORR
(95% CI, 27%-45%)

PEMAZYRE demonstrated a 36% ORR4

Image showing chart – PEMAZYRE demonstrated a 36% ORR: the primary endpoint

All evaluable patients N=107

Note: Data are from IRC per RECIST v1.1, and CR and PR are confirmed.

36% ORR
(95% CI, 27%-45%)

Duration of response (DoR)1

Image showing chart – 9.1 Months, Median DoR (95% CI, 6.0, 14.5) – 63% (n=24) of responders had a DoR ≥6 months and 18% (n=7) of responders had a DoR ≥12 months
 

CI, confidence interval; RECIST, Response Evaluation Criteria in Solid Tumors.

*The 95% CI was calculated using the Brookmeyer and Crowley's method.

 

FIGHT-202: Additional Endpoints

PEMAZYRE received accelerated approval from the FDA based on overall response rate and duration of response in a single-arm study

  • Progression-free survival, overall survival, and disease control rate were secondary endpoints that were studied in FIGHT-202 that are not reflected in the full Prescribing Information
  • Due to the potential variability in the natural history of the disease, a single-arm study may not adequately characterize these time-to-event endpoints
  • For this reason, a confirmatory Phase 3 study in cholangiocarcinoma is underway
 
Median PFS = 6.9 months
(95% CI, 6.2 to 9.6)

Progression-free Survival (PFS)4

Kaplan-Meier estimate of PFS (N=107)

Image showing chart – 6.9 Months, Median PFS= 6.9 months (95% CI, 6.2 to 9.6)
  • Median follow-up at time of data cutoff was 15.4 months.4
Median PFS = 6.9 months
(95% CI, 6.2 to 9.6)
 
Median OS = 21.1 months
(95% CI, 14.8 to NE)

Overall Survival (OS)4

Kaplan-Meier estimate of OS (N=107)

Image showing chart – 21.1 Months, Median OS=21.1 months (95% CI, 14.8 to NE)
  • At time of data cutoff: Median follow-up was 15.4 months; the OS data were not mature;
    a total of 40 patients (37%) had died.4
Median OS = 21.1 months
(95% CI, 14.8 to NE)

Disease Control Rate (DCR)4

Graphic of circle with text – 82% DCR (95% CI, 74 to 89)
DCR was defined as CR+PR+SD4
  • CR in 2.8% of patients (n=3); PR in 32.7% of patients (n=35); SD in 46.7% of patients (n=50)
  • FIGHT-202 was a single-arm study4
    • In this setting, the DCR results may reflect the natural history of cholangiocarcinoma in an individual patient, rather than the direct effect of treatment
 

PEMAZYRE:
FIGHT-202 Study Results

Hear from Dr Milind Javle as he presents PEMAZYRE efficacy data, including overall response rates from FIGHT-202.

PEMAZYRE : FIGHT-202
Study Results

Hear from Dr Milind Javle as he presents PEMAZYRE efficacy data, including overall response rates from FIGHT-202.

callout

References:

1. PEMAZYRE Prescribing Information. Incyte Corporation. 2. Data on file. Incyte Corporation. Wilmington, DE. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers V.5.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed September 21, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21(5):671-684.

INDICATIONS AND USAGE

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).

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 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 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, 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.

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]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment.

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 (60%), alopecia (49%), diarrhea (47%), nail toxicity (43%), fatigue (42%), dysgeusia (40%), nausea (40%), constipation (35%), stomatitis (35%), dry eye (35%), dry mouth (34%), decreased appetite (33%), vomiting (27%), arthralgia (25%), abdominal pain (23%), hypophosphatemia (23%), back pain (20%), and dry skin (20%).

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.

Reduce the recommended dose of PEMAZYRE for patients with severe renal impairment as described in the prescribing information.

Reduce the recommended dose of PEMAZYRE for patients with severe hepatic impairment as described in the prescribing information.

INDICATIONS AND USAGE

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).