A Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement - (FIGHT-203)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of pemigatinib (INCB054828) in subjects with myeloid/lymphoid neoplasms with fibroblast growth factor receptor (FGFR) 1 rearrangement.

Official Title
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A Phase 2, Open-Label, Monotherapy, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement - (FIGHT-203)

Conditions
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MPN (Myeloproliferative Neoplasms)

Intervention / Treatment
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* Drug: Pemigatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented lymphoid or myeloid neoplasm with 8p11 rearrangement known to lead to FGFR1 activation, based on standard diagnostic cytogenetic evaluation performed locally, before signing informed consent for this study. Eligible subjects must: Have relapsed after stem cell transplantation or after other disease modifying therapy, OR Not be current candidates for stem cell transplantation or other disease modifying therapies. Note: All relapsed/refractory subjects must have evidence of either cytogenetic or hematological disease and have no evidence of residual toxicity (eg, graft-versus-host disease requiring treatment). Life expectancy ≥ 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. Exclusion Criteria: Prior receipt of a selective FGFR inhibitor. History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, except calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcifications. Current evidence of corneal disorder/keratopathy, including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis, as confirmed by ophthalmologic examination. Use of any potent cytochrome P450 3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemigatinib<br> | Drug: Pemigatinib<br>* Pemigatinib once a day by mouth for 2 consecutive weeks and 1 week off therapy. Participants will receive either the intermittent dose (as written) or continuous dosing.<br>* Other names: INCB054828;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants who achieve Complete Response (CR) based on response criteria for myeloid/lymphoid neoplasms with FGFR1 rearrangement |  | : Assessed at protocol-defined timepoints through end of study, up to approximately 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects who achieve response, defined as a best response of CR or PR, as determined by investigator assessment according to the response criteria |  | Assessed at protocol-defined timepoints through end of study, up to approximately 24 months. | 
| The proportion of subjects who achieve a complete cytogenetic response (CCyR) as assessed by local analysis and investigator evaluation |  | Assessed at protocol-defined timepoints through end of study, up to approximately 24 months. | 
| The proportion of subjects who achieve a partial cytogenetic response (PCyR) as assessed by local analysis and investigator evaluation |  | Assessed at protocol-defined timepoints through end of study, up to approximately 24 months. | 
| Duration of CR, defined as the time from first assessment of CR to the earlier of disease progression or death due to any cause |  | Assessed at protocol-defined timepoints through end of study, up to approximately 24 months. | 
| Duration of response, defined as the time from first assessment of CR or PR to the earlier of disease progression or death due to any cause |  | Assessed at protocol-defined timepoints through end of study, up to approximately 24 months. | 
| Progression-free survival (PFS) | PFS is defined as the time from the first date of taking study drug until the date of disease progression, as measured by response criteria for myeloid/lymphoid neoplasms with FGFR1 rearrangement, or until death due to any cause, whichever is earlier. | From the date of first study drug dose until the date of disease progression or until death due to any cause, whichever is earlier, assessed up to approximately 24 months. | 
| Overall survival | Overall survival is defined as the time from the first day of taking study drug until death due to any cause. Subjects without death observed at the time of the analysis will be censored at last date known to be alive. | From date of first study drug dose until death due to any cause, assessed up to approximately 24 months. | 
| Safety and tolerability as assessed by frequency, duration, and severity of adverse events | A treatment-emergent AE was defined as an event occurring after exposure to at least 1 dose of study drug. A treatment-related AE was defined as an event with a definite, probable, or possible causality to study medication. A serious AE is an event resulting in death, hospitalization, persistent or significant disability/incapacity, or is life threatening, a congenital anomaly/birth defect or requires medical or surgical intervention to prevent 1 of the outcomes above. The intensity of an AE was graded according to the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (life-threatening). | From baseline through 30-35 days after end of treatment, up to 7 months per individual subject | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloid neoplasm, fibroblast growth factor receptor inhibitor, FGFR1 rearrangement, 8p11, eosinophilia, eosinophilic syndrome, Lymphoid neoplasm