August 26, 2022 - Pemigatinib (PEMAZYRE, Incyte Corporation) for adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement.

August 26, 2022

https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213736s002lbl.pdf

On August 26, 2022, the Food and Drug Administration approved pemigatinib (PEMAZYRE, Incyte Corporation) for adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement.

Efficacy was evaluated in FIGHT-203 (NCT03011372), a multicenter open-label, single-arm trial that included 28 patients with relapsed or refractory MLNs with FGFR1 rearrangement. Eligible patients were either not candidates for or have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or after a disease modifying therapy (e.g., chemotherapy). Pemigatinib was administered until disease progression, unacceptable toxicity, or until patients were able to receive allo-HSCT.

Selected demographics and baseline characteristics were: median age of 65 years (range, 39 to 78); 64% female; 68% White, 3.6% Black or African American, 11% Asian, and 3.6% American Indian/Alaska Native; and 88% ECOG performance status of 0 or 1.

Efficacy was established based on complete response (CR) rates per the response criteria relevant to the morphologic disease type. Of the 18 patients with chronic phase in the marrow with or without extramedullary disease (EMD), 14 achieved CR (78%; 95% CI: 52, 94). The median time-to-CR was 104 days (range, 44 to 435). The median duration was not reached (range: 1+ to 988+ days). Of the 4 patients with blast phase in the marrow with or without EMD, 2 achieved CR (duration: 1+ and 94 days). Of 3 patients with EMD only, 1 achieved a CR (duration: 64+ days). For all 28 patients (including 3 patients without evidence of morphologic disease), the complete cytogenetic response rate was 79% (22/28; 95% CI: 59, 92).

The most common (≥20%) adverse reactions occurring in patients 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 (≥10%) Grade 3 or 4 laboratory abnormalities were decreased phosphate, decreased lymphocytes, decreased leukocytes, decreased platelets, increased alanine aminotransferase, and decreased neutrophils.

The recommended pemigatinib dose is 13.5 mg orally once daily on a continuous basis until disease progression or unacceptable toxicity.

View full prescribing information for Pemazyre.

This application was granted priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. The application also was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email This email address is being protected from spambots. You need JavaScript enabled to view it..

April 17, 2020

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213736s000lbl.pdf.

On April 17, 2020, the Food and Drug Administration granted accelerated approval to pemigatinib (PEMAZYRE, Incyte Corporation) 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.

The FDA also approved the FoundationOne® CDX (Foundation Medicine, Inc.)  as a companion diagnostic for patient selection.

Efficacy was investigated in FIGHT-202 (NCT02924376), a multicenter open-label single-arm trial, in 107 patients with locally advanced unresectable or metastatic cholangiocarcinoma whose disease had progressed on or after at least one prior therapy and had an FGFR2 gene fusion or rearrangement (clinical trial assay performed at a central laboratory). Patients received pemigatinib, 13.5 mg orally, once daily for 14 consecutive days, followed by 7 days off therapy.

The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) determined by an independent review committee using RECIST 1.1. Among the 107 patients, the ORR was 36% (95% CI: 27%, 45%), including 3 complete responses. The median DOR was 9.1 months with responses lasting ≥ 6 months in 24 of the 38 (63%) responding patients and ≥ 12 months in 7 (18%) patients.

The most common adverse reactions to pemigatinib (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. Ocular toxicity and hyperphosphatemia are important risks of pemigatinib.

The recommended pemigatinib dose is 13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy in 21-day cycles.

View full prescribing information for PEMAZYRE.

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.

This application was granted priority review, breakthrough therapy and orphan drug designations. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email This email address is being protected from spambots. You need JavaScript enabled to view it..

For information on the COVID-19 pandemic, see the following resources:

• FDA: Coronavirus Disease 2019 (COVID-19)
• NCI: Coronavirus: What People With Cancer Should Know
• CDC: Coronavirus (COVID-19)

Follow the Oncology Center of Excellence on Twitter @FDAOncology

Pharmacist’s Applications to Practice

Pemigatinib for treatment of previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma (with susceptible FGFR2 genetic alteration)

Authors: Sidney Keisner, PharmD, BCOP
Associate Professor
University of Arkansas for Medical Sciences College of Pharmacy
Little Rock, AR

Leah Evans, PharmD Candidate
University of Arkansas for Medical Sciences College of Pharmacy
Little Rock, AR

What is the potential role for pemigatinib in the treatment of cholangiocarcinoma?

• Pemigatinib is an oral, selective fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor that inhibits FGFR1, 2, and 3. Disruption of FGFR signaling results in decreased proliferation and survival of malignant cells with FGFR genetic mutations. ¹
• Pemigatinib is indicated for previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma (CCA) with a FGFR2 genetic fusion or other rearrangement as detected by a United States Food and Drug Administration (FDA)-approved test. The FDA approved this drug under the accelerated approval process in April 2020 based on overall response rate and duration of response. Continued approval may be contingent upon verification of clinical benefit in a confirmatory trial.¹
• FDA approval was based on FIGHT-202, a phase II, open label, single arm trial (n=146) that evaluated pemigatinib in patients with locally advanced or metastatic CCA (with and without FGFR2 alterations) and disease progression after at least one prior therapy. Results from the cohort of patients with an FGFR2 fusion or rearrangement (n=107) are presented below:
  • The median age of the cohort with an FGFR2 fusion or rearrangement was 56 years, 61% of patients were female, 95% of patients had an ECOG performance status of 0 or 1, and 61% of patients had received only 1 prior therapy. Nearly all (98%) tumors were classified as intrahepatic.
  • Overall response rate was 35.5% including 2.8% of patients who achieved a complete response.
  • Median duration of response was 7.5 months.
  • Median progression free survival and overall survival were 6.9 and 21.1 months, respectively.²
• In the setting of previously-treated advanced biliary tract cancers, National Comprehensive Cancer Network (NCCN) guidelines list pemigatinib as “useful in certain circumstances” for patients with CCA and FGFR2 fusions or rearrangements (category 2A). Modified FOLFOX (mFOLFOX) is a preferred regimen (category 2A) in the overall population of previously-treated advanced biliary tract cancer patients based on a study that compared FOLFOX to active symptom control (n=162). FOLFOX was demonstrated to improve overall survival compared to the control arm (median 6.2 months versus 5.3 months; HR 0.69 (95% CI 0.5-0.97; p=0.031). The rate of overall survival at one year was 25.9% in the FOLFOX arm and 11.4% in the control arm.⁴
• Pemigatinib has not yet been directly compared to another treatment. FIGHT-302 (NCT03656536) is an open-label, randomized Phase III study which will compare efficacy and safety of first-line treatment with pemigatinib versus gemcitabine and cisplatin in patients with unresectable, metastatic CCA and a confirmed FGFR2 rearrangement.⁵

What role can the pharmacist play in the management of patients on pemigatinib?

• The recommended pemigatinib dose is 13.5 mg by mouth daily on days 1 to 14 of a 21-day cycle. Tablets should be swallowed whole and not crushed, split, chewed, or dissolved. Treatment continues until disease progression or unacceptable toxicity.¹
• Avoid use of moderate or strong CYP3A4 inhibitors or inducers with pemigatinib.
  • If concomitant use of a moderate or strong CYP3A4 inhibitor cannot be avoided, reduce dose by one dose level (13.5 mg to 9 mg or 9 mg to 4.5 mg).¹
• Dosage adjustments for mild/moderate renal or hepatic impairment are not required. Pemigatinib pharmacokinetics have not been studied in the setting of severe renal or hepatic impairment.¹
• The most common adverse events of any grade in the FIGHT-202 trial were hyperphosphatemia (55%), alopecia (46%), dysgeusia (38%), diarrhea (34%), fatigue (31%), dry mouth (29%), and stomatitis (27%).²
• Notable adverse effects include hyperphosphatemia and ocular toxicity.
  • Monitor serum phosphate levels during therapy. If the level is >5.5 mg/dl, a low phosphate diet should be initiated. If the level is >7 mg/dl, serum phosphate should be monitored weekly along with initiation of a phosphate binder. Depending on response to the phosphate binder, pemigatinib may be held, reduced, or permanently discontinued.¹
  • Retinal pigment epithelial detachment (RPED) occurred in 6% of patients in clinical trials. A baseline ophthalmologic exam including ocular coherence tomography should be performed prior to starting pemigatinib and repeated every 2 months for 6 months then every 3 months during the remainder of the treatment course. Onset of visual symptoms should prompt urgent referral for ophthalmologic examination.
    • Symptomatic or worsening RPED warrants holding and/or permanent discontinuation of therapy.¹
• Pemigatinib is solely dispensed by Biologics by McKesson specialty pharmacy.⁶
• IncyteCARES for Pemazyre is a manufacturer-based resource for patients and providers that provides educational and financial support and practice resources.⁶

Clinical Pearls

• FGFR2 alterations occur in 8 to 14% of intrahepatic CCAs.³
• FoundationOne CDx is the FDA approved companion diagnostic for pemigatinib and should be completed prior to initiating therapy to verify presence of an FGFR2 alteration.⁷
• If a dose is missed by 4 or more hours or vomiting occurs after a dose is taken, the patient should continue with the next scheduled dose. Additional doses should not be taken if a missed dose occurs.¹
• Pemigatinib should be taken at the same time every day and can be taken with or without food.¹
• Pemigatinib is available in 4.5 mg, 9 mg, and 13.5 mg tablets.¹
• Pemigatinib should be stored at room temperature (20-25°C).¹

References

1. Pemazyre. Package Insert. Incyte Pharmaceuticals Inc; 2020.
2. 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.
3. National Comprehensive Cancer Network. Hepatobiliary Tract Cancers (Version 5.2020). http://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. Accessed September 24, 2020.
4. Lamarca A, Palmer DH, Wasan HS, et al. A randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin / 5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced / metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. J Clinical Oncol. 2019;37 (no. 15_suppl):4003.
5. Bekaii-Saab TS, Valle JW, Cutsem EV, et al. FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements. Future Oncol. 2020 (published online ahead of print).
6. Incyte Corporation. IncyteCARES website. https://www.incytecares.com/. Accessed September 24, 2020.
7. Center for Devices and Radiological Health. List of Cleared or Approved Companion Diagnostic Devices. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-vitro-and-imaging-tools. Accessed September 24, 2020.