A Safety and Tolerability Study of Pemigatinib in Japanese Subjects With Advanced Malignancies - (FIGHT-102)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and tolerability of pemigatinib in Japanese subjects with advanced malignancies.

Official Title
-----------------
A Phase 1, Open-Label, Dose-Escalation, Dose-Expansion, Safety and Tolerability Study of Pemigatinib in Japanese Subjects With Advanced Malignancies - (FIGHT-102)

Conditions
-----------------
Solid Tumors

Intervention / Treatment
-----------------
* Drug: Pemigatinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: First generation Japanese; subject was born in Japan and has not lived outside of Japan for a total of > 10 years and subject can trace maternal and paternal Japanese ancestry. Part 1: Any histologically confirmed advanced solid tumor malignancy. Subjects enrolled at a lower dose level expansion cohort are required to have documented FGF/FGFR alterations and baseline and on-treatment tumor biopsy for testing of biomarkers. Part 2: Any histologically confirmed advanced solid tumor malignancy with a FGF/FGFR alteration Advanced or metastatic and recurrent cancer where an appropriate treatment option is not available. Life expectancy > 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status: Part 1: 0 or 1; Part 2: 0, 1, or 2. Genomic testing is mandatory for all enrolled subjects. Archival tumor specimen of at least 7 slides or willingness to undergo a pretreatment tumor biopsy to provide a tumor block or at least 7 unstained slides. Archival tumor biopsies are acceptable at baseline and should be no more than 2 years old (preferably less than 1 year old and collected since the completion of the last treatment); subjects with samples older than 2 years old and/or with sequencing report from the central laboratory require approval from the sponsor medical monitor for exemption from tumor biopsy or tumor sample requirement. Exclusion Criteria: Treatment with other investigational study drug for any indication for any reason, or receipt of anticancer medications within 21 days or 5 half-lives (whichever is longer) before first dose of study drug (6 weeks for mitomycin-C or nitrosoureas, 7 days for tyrosine kinase inhibitors). Prior receipt of a selective FGFR inhibitor. Laboratory and medical history parameters outside Protocol-defined range. History and/or current evidence of ectopic mineralization/calcification including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification. Current evidence of corneal disorder/keratopathy including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, confirmed by ophthalmologic examination.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>Part 1 is an open-label dose-escalation design based on observing each dose level for a period of 21 days. Part 2 will evaluate the recommended dose determined in Part 1. | Drug: Pemigatinib<br>* Pemigatinib at the protocol-defined dose administered once daily.<br>* Other names: INCB054828;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability assessed by monitoring frequency, duration, and severity of adverse events (AEs) | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a subject provides informed consent. | Baseline through 30 days after end of treatment, up to approximately 16 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate in subjects with measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Defined as proportion of subjects who meet the response criteria (complete response + partial response) as appropriate for the tumor type. | Baseline and Day 15 of every third treatment cycle, up to approximately 6 months | 
| Pharmacodynamics of pemigatinib assessed by changes in serum phosphorus level | Analyzed to look for differences that may be associated with response or safety as well as significant changes associated with treatment. | Baseline and protocol-defined timepoints throughout the treatment period, up to approximately 6 months | 
| Observed Plasma Concentration of pemigatinib | PK parameters will be calculated from the blood plasma concentrations of pemigatinib using standard noncompartmental (model independent) PK methods. | During the first cycle, up to Day 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Solid tumor, malignancy, fibroblast growth factor receptor (FGFR), fibroblast growth factor (FGF)/FGFR alteration