FDA Approves Pemigatinib for R/R FGFR1+ Myeloid/Lymphoid Neoplasms

Approval has been granted by the FDA to pemigatinib for the treatment of patients with myeloid/lymphoid neoplasms with FGFR1 rearrangement based on the phase 2 FIGHT-203 trial.

The FDA has approved pemigatinib (Pemazyre) for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) and FGFR1 rearrangement, according to Incyte.1

Findings from the phase 2 FIGHT-203 trial (NCT03011372), which examined the safety and efficacy of pemigatinib in 28 patients with relapsed or refractory MLNs with FGFR1 rearrangement, were the basis of the approval.

“In patients with relapsed or refractory MLNs with FGFR1 rearrangement treated with Pemazyre in FIGHT-203, the high rate of complete response and complete cytogenetic response in patients with chronic phase disease and the high rate of complete cytogenetic response in patients with blast phase disease is clinically meaningful, especially in light of the lack of these specific responses with existing first-line treatments,” said Srdan Verstovsek, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, and principal investigator for the FIGHT-203 study, in the press release.

In the study, pemigatinib demonstrated a complete response (CR) rate of 78% (95% CI, 52%-94%) in patients with chronic phase in the marrow with or without extramedullary disease (EMD; n = 18). The median time to CR for these patients was 104 days (range, 44-435), and the median duration of CR was not yet reached (range, 1+ to 988+ days).

“The approval of Pemazyre represents an important treatment advancement for people living with MLNs with FGFR1 rearrangement who currently have limited treatment options,” said Hervé Hoppenot, chief executive officer of Incyte, in a press release. “These are complex hematologic malignancies with a range of presentations, and this approval highlights Incyte’s continued leadership and commitment to advancing care for patients with rare blood cancers.”

In the multicenter open-label, single-arm trial, patients aged 18 years and older with relapsed or refractory MLNs with FGFR1 rearrangement could enroll. Eligibility was open to patients with documented lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation, who relapsed after stem cell transplantation or after other disease modifying therapy or were not current candidates for stem cell transplantation or other disease modifying therapies.2

Additionally, all relapsed/refractory subjects must have had evidence of cytogenetic or hematological disease and have no evidence of residual toxicity. Patients were required to have a life expectancy of 12 weeks or greater and an ECOG performance status 0, 1, or 2.

The primary end point of the trial was the proportion of participants who achieve CR with secondary end points including the proportion of subjects who achieve CR or PR, complete cytogenetic response, duration of CR, duration of response, progression-free survival, overall survival, safety, and tolerability.

Findings showed that among the patients with blast phase in the marrow with or without EMD (n = 4), 2 achieved a CR with pemigatinib. The duration of response ranged from 1 to 94 days. Of the patients with EMD only (n = 3), 1 patient achieved a CR at a duration of greater than 64 days.

For all 28 patients, including 3 patients without evidence of morphologic disease, the complete cytogenetic response rate achieved with pemigatinib was 79% (95% CI, 59%-92%).

In regard to safety, the most common adverse effects to be reported in 20% or more patients were hyperphosphatemia (74%), nail toxicity (62%), alopecia (59%), stomatitis (53%), diarrhea (50%), dry eye (50%), fatigue (44%), rash (35%), abdominal pain (35%), anemia (35%), constipation (32%), dry mouth (32%), epistaxis (29%), retinal pigment epithelial detachment (26%), extremity pain (26%), decreased appetite (24%), dry skin (24%), dyspepsia (24%), back pain (24%), nausea (21%), blurred vision (21%), peripheral edema (21%) and dizziness (21%).

“The approval of Pemazyre represents an important treatment advancement for people living with MLNs with FGFR1 rearrangement who currently have limited treatment options,” said Hervé Hoppenot, chief executive officer of Incyte, in a press release. “These are complex hematologic malignancies with a range of presentations, and this approval highlights Incyte’s continued leadership and commitment to advancing care for patients with rare blood cancers.”

References:

1. Incyte announces FDA approval of Pemazyre® (pemigatinib) as the first and only targeted treatment for myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. News release. Incyte. August 26, 2022. Accessed August 26, 2022. https://bwnews.pr/3wzSxxH

2. A study to evaluate the efficacy and safety of pemigatinib (INCB054828) in subjects with myeloid/lymphoid neoplasms with FGFR1 rearrangement - (FIGHT-203). ClinicalTrials.gov. Updated June 28, 2022. Accessed August 26, 2022. https://clinicaltrials.gov/ct2/show/NCT03011372