Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Relapsed or Refractory Advanced Non-Small Cell Lung Cancer With an FGFR Alteration

Study Overview
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Brief Summary
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This is an open-label, single arm study to study the safety, efficacy and tolerability of Pemigatinib when used on participants with squamous or nonsquamous NSCLC with a documented FGFR1-3 mutations or fusions/rearrangement who have progressed on prior therapies and have no available standard treatment options

Official Title
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A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Advanced Non-Small Cell Lung Cancer With an FGFR Alteration Who Progressed on Previous Therapy (FIGHT 210)

Conditions
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Non-Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Pemigatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed advanced or metastatic NSCLC (Stage IIIB/C or IV per the AJCC Cancer Staging Manual, 8th Edition). Both squamous and nonsquamous NSCLC are eligible. Radiographically measurable disease (per RECIST v1.1). Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measurable if progression has been clearly demonstrated in the lesion. Documentation of known/likely actionable known or likely FGFR1-3 alterations. Must have objective documented progression after at least 1 prior therapy, and must have no therapy available that is likely to provide clinical benefit. Participants who are intolerant of or decline the approved therapy are eligible only if they have no therapy available that is likely to provide clinical benefit. ECOG performance status of 0 to 2. Baseline archival tumor specimen (if less than 24 months from date of screening) or willingness to undergo a pretreatment tumor biopsy to obtain the specimen. Must be a tumor block or approximately 15 unstained slides from biopsy or resection of primary tumor or metastasis. Willingness to avoid pregnancy or fathering a child. Exclusion Criteria Prior receipt of a selective FGFR inhibitor. Receipt of anticancer medications or investigational drugs for any indication or reason within 28 days before the first dose of pemigatinib. Participants must have recovered (≤ Grade 1 as per CTCAE v5.0 or at pretreatment baseline) from AEs from previously administered therapies (excluding alopecia). Concurrent anticancer therapy (eg, chemotherapy, immunotherapy, biologic therapy, hormonal therapy, or investigational therapy). Candidate for potentially curative surgery. Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, and retinal detachment) as confirmed by ophthalmologic examination. Radiation therapy administered for the treatment of cancer lesions within 2 weeks before enrollment/first dose of study drug. Participants must have recovered from all radiation related toxicities, not require corticosteroids, and not have had radiation pneumonitis. Evidence of fibrosis within a radiation field from prior radiotherapy is permitted with medical monitor approval. A 1-week washout is permitted for palliative radiation to non-CNS disease. Untreated brain or CNS metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases). Participants who have previously treated and clinically stable brain or CNS metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period, and if they are on a stable or decreasing dose of corticosteroids for at least 1 week. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Participants with defined laboratory values at screening. History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance). History of hypovitaminosis D requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants enrolled in this study will be assigned to 1 of 2 cohorts: Cohort A (squamous NSCLC) will enroll approximately 100 participants, and Cohort B (nonsquamous NSCLC) will enroll approximately 25 participants.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Squamous NSCLC<br>Participants with squamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements will receive intermittent dosing. | Drug: Pemigatinib<br>* 13.5 mg tablet<br>* Other names: INCB 54828;|
| Experimental: Cohort B: Non-squamous NSCLC<br>Participants with non-squamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements will receive intermittent dosing. | Drug: Pemigatinib<br>* 13.5 mg tablet<br>* Other names: INCB 54828;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Overall Response Rate (ORR) | Defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) based on RECIST v1.1. Response will be determined by an Independent Central Radiology (ICR) review. | Up to approximately 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort B: ORR | Defined as the proportion of participants who achieve a CR or PR based on RECIST v1.1. Response will be determined by an ICR review. | Up to approximately 9 months | 
| Cohort A: Progression-Free Survivol (PFS) | Defined as the time from the first dose of study drug until Progressive Disease (PD) (according to RECIST v1.1 as assessed by an ICR review) or death, whichever is first. | Up to approximately 9 months | 
| Cohort A: Duration of Response (DOR) | Defined as the time from the date of the first CR or PR until the date of the first PD (according to RECIST v1.1 as assessed by an ICR review) or death, whichever is first. | Up to approximately 9 months | 
| Cohort A: Overall Survival (OS) | Defined as the time from the first dose of study drug to death of any cause. | Up to approximately 9 months | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | TEAE is any Adverse Event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to approximately 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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squamous NSCLC, Advanced Non-Small Cell Lung Cancer (NSCLC), fibroblast growth factor receptor (FGFR), FGFR1-3 mutations, FGFR1-3 fusions, FGFR1-3 rearrangements, nonsquamous NSCLC, relapsed or refractory