A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the efficacy of erdafitinib in terms of overall response rate (ORR) in adult and pediatric participants with advanced solid tumors with fibroblast growth factor receptor (FGFR) alterations (mutations or gene fusions). It will also evaluate ORR in pediatric participants with advanced solid tumors and FGFR alterations.

Detailed Description
-----------------
Erdafitinib is a selective and potent pan FGFR 1-4 inhibitor with demonstrated clinical activity in participants with metastatic urothelial cancer and cholangiocarcinoma identified to have alterations in the FGFR pathway. This study targets the underlying altered biology of FGFR-driven tumors irrespective of solid tumor histology subtype. The study consists of screening phase, treatment phase and the post treatment follow-up phase (from the end of treatment visit until the participant has died, withdraws consent, is lost to follow-up, or the end of study, whichever comes first). End of study is considered as the time when the last participant receives the last dose of study drug on the study and either all pediatric participants are off study or until the most recently enrolled pediatric participant still participating in the study has 6 months of follow-up, whichever occurs first. Currently this study is recruiting pediatric participants only.

Official Title
-----------------
A Phase 2 Study of Erdafitinib in Subjects With Advanced Solid Tumors and FGFR Gene Alterations

Conditions
-----------------
Advanced Solid Tumor

Intervention / Treatment
-----------------
* Drug: Erdafitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologic demonstration of an unresectable, locally advanced, or metastatic solid tumor malignancy with an fibroblast growth factor receptor (FGFR) mutation or FGFR gene fusion Measurable disease Participant must have received at least one prior line of systemic therapy in the advanced, unresectable, or metastatic setting; or is a child or adolescent participant with a newly-diagnosed solid tumor and no acceptable standard therapies Documented progression of disease, defined as any progression that requires a change in treatment, prior to full study screening Exclusion Criteria: Has had prior chemotherapy, targeted therapy, or treatment with an investigational anticancer agent within 15 days or less than or equal to (<=) 5 half-lives of the agent (whichever is longer) and up to a maximum of 30 days before the first dose of erdafitinib The presence of FGFR gatekeeper and resistance mutations Histologic demonstration of urothelial carcinoma Hematologic malignancy (i.e., myeloid and lymphoid neoplasms For non-small cell lung cancer participants only: pathogenic somatic mutations or gene fusions in the following genes: EGFR, ALK, ROS1, NTRK, BRAF V600E and KRAS Active malignancies other than for disease requiring therapy

Ages Eligible for Study
-----------------
Minimum Age: 6 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: Erdafitinib<br>Participants with fibroblast growth factor receptor (FGFR) mutations and FGFR gene fusions will receive a dose of erdafitinib oral tablets until disease progression, intolerable toxicity, withdrawal of consent, decision by the investigator to discontinue treatment, or end of data collection timepoint if there is clinical benefit in the opinion of the investigator, has been achieved. | Drug: Erdafitinib<br>* Participants will receive erdafitinib oral tablets.<br>* Other names: JNJ-42756493;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) as Assessed by Independent Review Committee (IRC) | ORR as assessed by IRC is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR). | Up to 6 years and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate as Assessed by Investigator | ORR as assessed by investigator is defined as the percentage of participants who achieve a CR or PR. | Up to 6 years and 9 months | 
| Duration of Response (DOR) | DOR is the duration from the date of initial documentation of a response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study), or death, whichever comes first. | Up to 6 years and 9 months | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of participants with CR, PR or stable disease (SD). | Up to 6 years and 9 months | 
| Clinical Benefit Rate (CBR) | CBR is defined as the percentage of participants with CR, PR or durable SD. | Up to 6 years and 9 months | 
| Progression Free Survival (PFS) | PFS is the duration from the date of the first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first. | Up to 6 years and 9 months | 
| Overall Survival (OS) | OS will be measured from the date of first dose of study drug to the date of the participant's death. | Up to 6 years and 9 months | 
| Plasma Concentrations of Erdafitinib | Plasma concentrations of erdafitinib will be reported. | Predose and 2-4 hours postdose | 
| Number of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the relevant investigational product. | Up to 6 years and 9 months | 
| Number of Participants with Adverse Events by Severity | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Adverse event severity is a clinical determination of the intensity of an adverse event. | Up to 6 years and 9 months | 
| Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score | The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms. | Baseline; up to 2 years and 9 months | 
| Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score | The PGIS is a single question regarding the patient report of disease severity: considering all aspects of your cancer symptoms right now would you say your cancer symptoms are none, mild, moderate, severe, or very severe? | Baseline; up to 2 years and 9 months | 
| Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Change (PGIC) Scale | The PGIC is the patient-reported outcome (PRO) counterpart to the clinical global impressions (CGI) scale. The PGIC is a single verbal rating scale ranging from 1 = a lot better now to 7 = a lot worse now. | Baseline; up to 2 years and 9 months | 
| Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score | The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating health today with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). | Baseline; up to 2 years and 9 months | 
| Change from Baseline in Pediatric Functional Assessment of Cancer Therapy - Brain (Peds FACT-Br) Total Score | Peds FACT-Br consists of 4 sets of disease-specific questions pertaining to brain neoplasms (a set of 34 to 37 questions each for child, parent of child, adolescent or parent of adolescent). Peds FACT-Br total score for child ranges from 0-136 and for parent of child, adolescent and parent of adolescent the score ranges from 0-148. Here '0' indicates a severely symptomatic participant and highest score indicates asymptomatic participant. | Baseline; up to 2 years and 9 months |