A Study of Erdafitinib in Participants With Advanced Solid Tumors and Fibroblast Growth Factor Receptor (FGFR) Gene Alterations
- Registration Number
- NCT04083976
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 316
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Erdafitinib Erdafitinib 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.
- Primary Outcome Measures
Name Time Method Broad Panel and Pediatric Cohorts: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 4 years ORR is defined as the percentage of participants who achieved a complete response (CR), or partial response (PR) based on Response Assessment in Neuro-Oncology (RANO) criteria. According to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions; PR: sum of products of diameters \[SPD\] decreased by \>=50 percent \[%\] from baseline value) and clinical performance status with steroid dose information.
Core Panel Cohort: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 4 years ORR is defined as the percentage of participants who achieved a CR, or PR based on RANO criteria. According to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions; PR: sum of products of diameters \[SPD\] decreased by \>=50 percent \[%\] from baseline value) and clinical performance status with steroid dose information. The core panel cohort is a subgroup of the broad panel cohort with a select panel of pre-specified FGFR markers: FGFR3 mutations (S249C;Y373C; R248C; G370C); FGFR2 mutations (C382R); FGFR3 fusions (FGFR3-TACC3); FGFR2 fusions (FGFR2-BICC1; FGFR2-TACC2).
- Secondary Outcome Measures
Name Time Method Clinical Benefit Rate (CBR) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Progression-free Survival (PFS) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Objective Response Rate (ORR) as Assessed by Investigators Assessment Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Duration of Responses (DOR) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Disease Control Rate (DCR) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Overall Survival (OS) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Number of Participants With Adverse Events (AEs) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Number of Participants With Adverse Events (AEs) by Severity Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Pediatric Cohort: Plasma Concentration of Erdafitinib Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) for Participants >=18 Years Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Change From Baseline in Pediatric Functional Assessment Of Cancer Therapy-Brain (Peds FACT-Br) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Change From Baseline in Patient Global Impression of Symptom Severity (PGIS) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Change From Baseline in Patient Global Impression of Change (PGIC) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months Change From Baseline in European Quality of Life -5 Dimensions-5 Levels (EQ-5D-5L) Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months
Trial Locations
- Locations (171)
Arizona Oncology Associates, PC - HOPE
🇺🇸Tucson, Arizona, United States
Rocky Mountain Cancer Centers
🇺🇸Colorado Springs, Colorado, United States
Memorial Cancer Institute
🇺🇸Hollywood, Florida, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Hawaii Cancer Care
🇺🇸'Aiea, Hawaii, United States
Maine Medical Center
🇺🇸Scarborough, Maine, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Scroll for more (161 remaining)Arizona Oncology Associates, PC - HOPE🇺🇸Tucson, Arizona, United States