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

Conditions

Advanced Solid Tumor

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.

Carranza O, Pant S, Schuler M, Witt O, Geoerger B, Loriot Y, Farouk Sait S, Arnold D, Dal Molin GZ, Lugowska I, Winter H, Baldini C, Corassa M, Thomas S, Crow L, Xia Y, Triantos S, Sweiti H, Reardon DA.

2026-07-15

10.1200/po-25-01094

Efficacy and safety of erdafitinib in adults with NSCLC and prespecified fibroblast growth factor receptor alterations in the phase 2 open-label, single-arm RAGNAR trial.

Martin Schüler, Josep Tabernero, Omar Carranza, Yohann Loriot, Shubham Pant et al. (19 authors)

Journal of Clinical Oncology2024-06-014 citations

10.1200/jco.2024.42.16_suppl.8515

Efficacy and safety of erdafitinib in pediatric patients with advanced solid tumors and FGFR alterations in the phase 2 RAGNAR trial.

Olaf Witt, Sameer Farouk Sait, Blanca Diez, Agustin Cardoso, David A. Reardon et al. (18 authors)

Journal of Clinical Oncology2024-06-014 citations

10.1200/jco.2024.42.16_suppl.10002

Efficacy of erdafitinib in adults with advanced solid tumors and non-prespecified fibroblast growth factor receptor mutations in the phase 2 RAGNAR trial: Exploratory cohort.

Iwona Ługowska, Martin Schüler, Yohann Loriot, Omar Carranza, Gopa Iyer et al. (20 authors)

Journal of Clinical Oncology2024-06-011 citations

10.1200/jco.2024.42.16_suppl.3119

Efficacy and safety of erdafitinib in patients with advanced or metastatic cholangiocarcinoma and FGFR alterations: Pooled analysis of RAGNAR and LUC2001 studies.

Shubham Pant, Joon Oh Park, Wu‐Chou Su, Martin Schüler, Yohann Loriot et al. (20 authors)

Journal of Clinical Oncology2024-06-011 citations

10.1200/jco.2024.42.16_suppl.4121

Efficacy and safety of erdafitinib in adults with breast cancer and prespecified fibroblast growth factor receptor alterations in the phase 2 open-label, single-arm RAGNAR trial.

Omar Carranza, Martin Schüler, Josep Tabernero, Yohann Loriot, Dirk Arnold et al. (19 authors)

Journal of Clinical Oncology2024-06-011 citations

10.1200/jco.2024.42.16_suppl.1088

Development of a novel RNA-based fibroblast growth factor receptor response signature (FGFR-PRS) for use in patients with urothelial cancer (UC).

Kirk L. Pappan, Gregory M. Mayhew, James M. Davison, Yoichiro Shibata, Joel R. Eisner et al. (7 authors)

Journal of Clinical Oncology2024-01-29

10.1200/jco.2024.42.4_suppl.548

Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study.

Pant S, Schuler M, Iyer G, Witt O, Doi T, Qin S, Tabernero J, Reardon DA, Massard C, Minchom A, Lugowska I, Carranza O, Arnold D, Gutierrez M, Winter H, Stuyckens K, Crow L, Najmi S, Hammond C, Thomas S, Santiago-Walker A, Triantos S, Sweiti H, Loriot Y, RAGNAR Investigators.

2023-08-01145 citations

10.1016/s1470-2045(23)00275-9

Tumor agnostic efficacy and safety of erdafitinib (erda) in patients (pts) with advanced solid tumors with prespecified FGFR alterations (FGFRalt): RAGNAR primary analysis.

Shubham Pant, Martin Schüler, Gopa Iyer, Olaf Witt, Toshihiko Doi et al. (20 authors)

Journal of Clinical Oncology2023-06-017 citations

10.1200/jco.2023.41.16_suppl.3121

Efficacy and safety of erdafitinib in adults with cholangiocarcinoma (CCA) with prespecified fibroblast growth factor receptor alterations (FGFRalt) in the phase 2 open-label, single-arm RAGNAR trial: Expansion cohort results.

Shubham Pant, Martin Schüler, Gopa Iyer, Toshihiko Doi, Shukui Qin et al. (20 authors)

Journal of Clinical Oncology2023-01-2417 citations

10.1200/jco.2023.41.4_suppl.610

Tumor agnostic efficacy and safety of erdafitinib in patients (pts) with advanced solid tumors with prespecified fibroblast growth factor receptor alterations (FGFRalt) in RAGNAR: Interim analysis (IA) results.

Yohann Loriot, Martin Schüler, Gopa Iyer, Olaf Witt, Toshihiko Doi et al. (20 authors)

Journal of Clinical Oncology2022-06-0144 citations

10.1200/jco.2022.40.16_suppl.3007

Erdafitinib in pediatric patients with advanced solid tumors with fibroblast growth factor receptor (FGFR) gene alterations: RAGNAR study pediatric cohort.

Olaf Witt, Birgit Geoerger, Uta Dirksen, Sameer Farouk Sait, David A. Reardon et al. (15 authors)

Journal of Clinical Oncology2022-06-012 citations

10.1200/jco.2022.40.16_suppl.tps10058

Preliminary results of molecular screening for FGFR alterations (alts) in the RAGNAR histology-agnostic study with the FGFR-inhibitor (FGFRi) erdafitinib.

Christophe Massard, Shubham Pant, Gopa Iyer, Martin Schüler, Olaf Witt et al. (15 authors)

Journal of Clinical Oncology2021-05-203 citations

10.1200/jco.2021.39.15_suppl.4081

A phase II open-label study in adult and adolescent patients (pts) with advanced solid tumors harboring fibroblast growth factor receptor (FGFR) gene alterations.

Shubham Pant, Josep Tabernero, Christophe Massard, Gopa Iyer, Olaf Witt et al. (17 authors)

Journal of Clinical Oncology2021-01-20

10.1200/jco.2021.39.3_suppl.tps480

Interventions

DRUGErdafitinib

Participants will receive erdafitinib oral tablets.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame
Objective Response Rate (ORR) as Assessed by Investigator 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
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
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
Plasma Concentration of Erdafitinib	Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months
Broad Panel, CCA Expansion, and Exploratory Cohorts: Change From Baseline in European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30)	Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 5 years 4 months
Pediatric Cohorts: 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

Countries

Argentina, Australia, Belgium, Brazil, China, France, Germany, Italy, Japan, Poland, South Korea, Spain, Taiwan, United Kingdom, United States

Contacts

STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial

Janssen Research & Development, LLC

Participant flow

Pre-assignment details

As pre-specified in the protocol, adolescent participants enrolled in the Broad Panel Cohort who met the pediatric cohort definition were planned to be analyzed as part of the Broad Panel Cohort and the Pediatric Cohort. 2 adolescent participants from the broad panel cohort were included in the pediatric cohort. Hence, these 2 participants are counted as enrolled twice (once in Broad Panel Cohort and once in Pediatric Cohort).

Participants by arm

Arm	Count
Broad Panel Cohort Adolescent and adult participants with target fibroblast growth factor receptor (FGFR) mutations or any FGFR gene fusions, were enrolled in this cohort. Adolescent participants aged greater than or equal to (\>=)12 to less than (\<)15 years received erdafitinib 5 milligrams (mg) once daily orally, with possible up-titration to 6 mg or further to 8 mg based on Cycle 1 Day 14 and Cycle 2 Day 7 (each cycle of 21 days) serum phosphate levels. Adolescent participants aged \>=15 to \<18 years and adults participants aged 18 years and older received erdafitinib 8 mg once daily orally, with possible up-titration to 9 mg or maintenance at 8 mg daily based on Cycle 1 Day 14 serum phosphate levels.	217
Cholangiocarcinoma (CCA) Expansion Cohort Adolescent and adult participants with target FGFR mutations or any FGFR gene fusion once the broad panel cohort has reached the cap of approximately 30 participants for cholangiocarcinoma, were enrolled in this cohort. Adolescent participants aged \>=12 to \<15 years received erdafitinib 5 mg once daily orally, with possible up-titration to 6 mg or further to 8 mg based on Cycle 1 Day 14 and Cycle 2 Day 7 (each cycle of 21 days) serum phosphate levels. Adolescent participants aged \>=15 to \<18 years and adults participants aged 18 years and older received erdafitinib 8 mg once daily orally, with possible up-titration to 9 mg or maintenance at 8 mg daily based on Cycle 1 Day 14 serum phosphate levels.	35
Exploratory Cohort Adolescent and adult participants with any other FGFR mutations that are not captured in the broad panel cohort, were enrolled in this cohort. Adolescent participants aged \>=12 to \<15 years received erdafitinib 5 mg once daily orally, with possible up-titration to 6 mg or further to 8 mg based on Cycle 1 Day 14 and Cycle 2 Day 7 (each cycle of 21 days) serum phosphate levels. Adolescent participants aged \>=15 to \<18 years and adults participants aged 18 years and older received erdafitinib 8 mg once daily orally, with possible up-titration to 9 mg or maintenance at 8 mg daily based on Cycle 1 Day 14 serum phosphate levels.	53
Pediatric Cohort Children and adolescent (from Broad Panel cohort) participants with locally advanced or metastatic solid tumors harboring FGFR alterations, any gene fusions or FGFR internal tandem duplication who had either progressed on prior therapies and who had no acceptable standard therapies, or who had a newly diagnosed solid tumor and who had no acceptable standard therapies, were enrolled in this cohort. Children aged \>=6 to \<12 years received erdafitinib 3 mg once daily orally, with possible up-titration to 4 mg or further to 5 mg based on Cycle 1 Day 14 and Cycle 2 Day 7 (each cycle of 21 days) serum phosphate levels. Adolescent participants aged \>=12 to \<15 years received erdafitinib 5 mg once daily orally, with possible up-titration to 6 mg or further to 8 mg based on Cycle 1 Day 14 and Cycle 2 Day 7 serum phosphate levels, Adolescent participants aged \>=15 to \<18 years received erdafitinib 8 mg once daily orally, with possible up-titration to 9 mg or maintenance at 8 mg daily based on Cycle 1 Day 14 serum phosphate levels.	11
Total	316

Baseline characteristics

Characteristic	Broad Panel Cohort	Cholangiocarcinoma (CCA) Expansion Cohort	Total	Exploratory Cohort	Pediatric Cohort
AgeContinuous	55.6 years STANDARD_DEVIATION 13.51	57 years STANDARD_DEVIATION 9.94	55 years STANDARD_DEVIATION 15.07	60 years STANDARD_DEVIATION 11.74	12.4 years STANDARD_DEVIATION 2.98
Age, Customized 12 years to <18 years	2 Participants	0 Participants	9 Participants	0 Participants	7 Participants
Age, Customized 18 years to <65 years	162 Participants	25 Participants	218 Participants	31 Participants	0 Participants
Age, Customized 65 years and over	53 Participants	10 Participants	85 Participants	22 Participants	0 Participants
Age, Customized 6 years to <12 years	0 Participants	0 Participants	4 Participants	0 Participants	4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants	1 Participants	15 Participants	0 Participants	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	173 Participants	27 Participants	256 Participants	52 Participants	4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	35 Participants	7 Participants	45 Participants	1 Participants	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	57 Participants	11 Participants	94 Participants	24 Participants	2 Participants
Race (NIH/OMB) Black or African American	6 Participants	0 Participants	12 Participants	4 Participants	2 Participants
Race (NIH/OMB) More than one race	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	38 Participants	6 Participants	46 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	112 Participants	18 Participants	160 Participants	25 Participants	5 Participants
Region of Enrollment ARGENTINA	2 Participants	0 Participants	6 Participants	0 Participants	4 Participants
Region of Enrollment AUSTRALIA	12 Participants	2 Participants	18 Participants	4 Participants	0 Participants
Region of Enrollment BELGIUM	10 Participants	5 Participants	22 Participants	7 Participants	0 Participants
Region of Enrollment BRAZIL	8 Participants	1 Participants	10 Participants	0 Participants	1 Participants
Region of Enrollment CHINA	12 Participants	3 Participants	15 Participants	0 Participants	0 Participants
Region of Enrollment FRANCE	26 Participants	5 Participants	32 Participants	0 Participants	1 Participants
Region of Enrollment GERMANY	22 Participants	4 Participants	30 Participants	4 Participants	0 Participants
Region of Enrollment ITALY	3 Participants	0 Participants	3 Participants	0 Participants	0 Participants
Region of Enrollment JAPAN	23 Participants	3 Participants	30 Participants	2 Participants	2 Participants
Region of Enrollment POLAND	3 Participants	0 Participants	6 Participants	3 Participants	0 Participants
Region of Enrollment SOUTH KOREA	6 Participants	1 Participants	14 Participants	7 Participants	0 Participants
Region of Enrollment SPAIN	16 Participants	3 Participants	26 Participants	6 Participants	1 Participants
Region of Enrollment TAIWAN	12 Participants	4 Participants	31 Participants	15 Participants	0 Participants
Region of Enrollment UNITED KINGDOM	14 Participants	1 Participants	19 Participants	4 Participants	0 Participants
Region of Enrollment UNITED STATES	48 Participants	3 Participants	54 Participants	1 Participants	2 Participants
Sex: Female, Male Female	97 Participants	23 Participants	159 Participants	32 Participants	7 Participants
Sex: Female, Male Male	120 Participants	12 Participants	157 Participants	21 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	8 / 217	1 / 35	1 / 53	1 / 11
other Total, other adverse events	215 / 217	35 / 35	53 / 53	11 / 11
serious Total, serious adverse events	86 / 217	15 / 35	26 / 53	8 / 11

Outcome results

Primary

Broad Panel and Pediatric Cohorts: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC)

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.

Time frame: Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 4 years

Population: The treated population consisted of all participants in broad panel and pediatric cohorts who received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
Broad Panel Cohort	Broad Panel and Pediatric Cohorts: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC)	29.5 Percentage of participants
Pediatric Cohort	Broad Panel and Pediatric Cohorts: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC)	66.7 Percentage of participants

Primary

Core Panel Cohort: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC)

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).

Time frame: Baseline (Cycle 1 Day 1 [each cycle of 21 days]) up to 4 years

Population: The treated population (core panel) consisted of a subgroup of participants in the broad panel cohort (fibroblast growth factor receptor \[FGFR+\]) with a select panel of pre-specified FGFR markers who received at least 1 dose of study drug.

Arm	Measure	Value (NUMBER)
Broad Panel Cohort	Core Panel Cohort: Objective Response Rate (ORR) Based on Response Assessment in Neuro-Oncology (RANO) as Assessed by Independent Review Committee (IRC)	26.6 Percentage of participants

Secondary