Advanced solid tumors (other than Urothelial tumors), and FGFR gene alterations. MedDRA version: 21.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. =12 years of age 2. Criterion modified per Amendment 1 2.1 Criterion modified per Amendment 2 2.2 Histologic demonstration of an unresectable, locally advanced, or metastatic solid tumor malignancy bearing an FGFR mutation or fusion, as determined by local* or central laboratory screening (Section 8.1.1.1). *Subjects with target FGFR mutations or any** FGFR gene fusions are eligible for enrollment in the Broad Panel Cohort (The List of Target FGFR Mutations is provided in Section 10.11) *Subjects with other FGFR mutations*** not captured in the Broad Panel Cohort are eligible for enrollment in the Exploratory Cohort. * Locally performed or commercial testing results from tissue or blood with NGS tests,direct digital counting methods, or the Qiagen therascreen® FGFR RT-PCR test performed in Clinical laboratory Improvement Amendments (CLIA)-certified or regional equivalent laboratories. **FGFR gene fusions: - Have a report suggesting the presence of an intact FGFR kinase domain. - FGFR fusion with a 3-prime partner (FGFR gene is listed first, eg FGFR-GENE or FGFR3-TACC3): -The FGFR portion of the fusion must involve exon 17 or greater (=17) - FGFR fusion with a 5-prime partner (Partner gene is listed first and FGFR gene is second, eg GENE-FGFR or KLK2-FGFR2): - The FGFR portion of the fusion must involve less than or equal to exon 11 (=11) - Have a named FGFR fusion partner gene (self-fusions or rearrangements, eg FGFR-FGFR, are not eligible) - FGFR gene identifiers, canonical transcript identifiers, and kinase domain positions are provided below for reference (see protocol) 3. Measurable disease according to RECIST v1.1 or RANO for primary brain tumors. 4. Criterion modified per Amendment 2 4.1 Subject must have received at least one prior line of systemic therapy in the advanced, unresectable, or metastatic setting. 5. Subject does not have standard of care options that have shown meaningful clinical benefit for the relevant underlying histology and line of therapy or the subject is unable to tolerate the therapy 6. Documented progression of disease, defined as any progression that requires a change in treatment, prior to full study screening 7. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia, peripheral neuropathy, and Grade 2 laboratory values eligible per Inclusion Criterion 9. 8. For adults (=18 years of age), ECOG performance status Grade 0 or 1 (Section 10.5) For adolescents (=12 to 1.5xULN -Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5x institutional ULN or =5x institutional ULN for subjects with liver metastases c. Renal function: Creatinine clearance(CrCl) >30 mL/min calculated using the Cockcroft-Gault formula for adult subjects or the CKiD (Chronic Kidney Disease in Children)Schwartz formula for adolescent subjects (Se
Exclusion criteria
Exclusion criteria: 1.Criterion modified per Amendment 2 1.1 Has had prior chemotherapy, targeted therapy, or treatment with an investigational anticancer agent within 15 days or =5 half-lives of the agent (whichever is longer)and up to a maximum of 30 days before the first dose of erdafitinib. Has had prior monoclonal antibody or immunotherapy within 30 days before the first dose of erdafitinib and/or has an ongoing Grade =2 immunotherapyrelated toxicity 2.Criterion modified per Amendment 2 2.1 The known*presence of FGFR gatekeeper and resistance alterations. Mutations in the following positions: FGFR1 V561; FGFR2 V564; FGFR2 N549; FGFR3 V555; and FGFR4 V550 *Observation of a gatekeeper/resistance alteration in the local or central report. If the test does not screen for all four FGFRs, eg FGFR4, the local report remains evaluable for molecular screening. 3. Criterion modified per Amendment 1 3.1 Criterion modified per Amendment 2 3.2. For NSCLC subjects only - pathogenic somatic mutations in EGFR* or BRAF V600E, or any gene fusions in the following genes: ALK, ROS1 or NTRK. *Assessment of these genes may be performed per institutional standard and do not have to be assessed via NGS. 4.Criterion modified per Amendment 2 4.1 Histologic demonstration of urothelial carcinoma. 5. Hematologic malignancy (ie, myeloid and lymphoid neoplasms) 6. Active malignancies other than for disease requiring therapy 7. Symptomatic central nervous system metastases (except for subjects with primary CNS tumors) 8. Criterion modified per Amendment 2 8.1 Received prior selective inhibitor treatment 9. Known allergies, hypersensitivity, or intolerance to erdafitinib or its excipients. 10. Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade. 11. Criterion modified per Amendment 1 11.1. Criterion modified per Amendment 2 11.2. History of uncontrolled cardiovascular disease include: -Unstable angina, myocardial infarction, ventricular fibrillation, Torsades de Pointes, cardiac arrest, or known congestive heart failure Class III-IV (Section 10.8) within the preceding 3 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months. -QTc prolongation (Fridericia: QTc >480 milliseconds; or for adolescent subjects, Bazett: QTc >440 milliseconds) 12. Known history of AIDS (human immunodeficiency virus [HIV] infection), unless the subject has been on a stable anti-retroviral therapy regimen for the last 6 months or more, has had no opportunistic infections in the last 6 months, and has CD4 count >350. 13. Criterion modified per Amendment 1 13.1 Criterion modified per Amendment 2 13.2. Evidence of active hepatitis B or C infection (for example, subjects with history of hepatitis C infection but normal hepatitis C virus polymerase chain reaction [PCR] test and subjects with inactive hepatitis B with positive HBsAg antibody or normal PCR are allowed) 14. Not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, neuropathy, hearing loss). 15. Impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions. 16. Major surgery within 4 weeks before first dose of erdafitinib. 17. Criterion modified per Amendment 2 17.1 Palliative radiation to the target lesion within 2 weeks before the first dose of erdafitinib. 18. Pregnant, or breast-feeding, or plan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of erdafitinib in terms of overall response rate (ORR) as assessed by the Independent Review Committee (IRC) in subjects with advanced solid tumors with target FGFR mutations and any gene fusions (Broad Panel Cohort), or in a pre-specified subgroup of subjects with a selected panel of FGFR markers (Core Panel Cohort), or in both cohorts;Secondary Objective: - To evaluate the efficacy of erdafitinib, in terms of the ORR, as assessed by investigator - To evaluate the efficacy of erdafitinib in terms of DOR - To evaluate other measures of efficacy including DCR, PFS, and OS - To evaluate erdafitinib PK - To evaluate Health-Related Quality of Life Cholangiocarcinoma Expansion Cohort -To evaluate the efficacy and safety of erdafitinib in subjects with cholangiocarcinoma with target FGFR mutations and any gene fusions;Primary end point(s): The proportion of subjects who achieve a complete response (CR) or partial response (PR) based on RECIST v1.1. or RANO as assessed by IRC;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The proportion of subjects who achieve a CR or PR based on RECIST v1.1. or RANO as assessed by investigator - DOR: the duration from the date of initial documentation of a response to the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever comes first. Data from subjects who are progression-free and alive or have unknown status will be censored at the last tumor assessment - DCR: the proportion of subjects with CR, PR or stable disease SD - PFS: 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 subjects who experience CR during the study) or death, whichever comes first. Data from subjects who are progression-free and alive or have unknown status will be censored at the last tumor assessment - OS: measured from the date of first dose of study drug to the date of the subject’s death. If the subject is alive or the vital status is unknown, the subject’s data will be censored at the date the subject was last known to be alive - PK exposure parameters.This endpoint includes pediatrics. - Incidence and severity of AEs - Change from baseline in patient-reported health status and physical functioning scales of the EORTC-QLQ-C30, PGIS, PGIC, and EQ-5D-5L. Cholangiocarcinoma Expansion Cohort - Key efficacy endpoints will be evaluated including ORR assessed by IRC/investigator, DOR, PFS, and OS - Incidence and severity of AEs ;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Argentina, Australia, Belgium, Brazil, China, France, Germany, Italy, Japan, Korea, Republic of, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed