A Phase 2 Study of Erdafitinib in Subjects with Advanced Solid Tumors and FGFR Gene Alterations
- Conditions
- Advanced solid tumors (other than Urothelial tumors), and FGFR genealterations.Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-510301-18-00
- Lead Sponsor
- Janssen Cilag International
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 11
1. Criterion modified per Amendment 3 1.1 =6 years of age., 9. Criterion modified per Amendment 1,Amendment 2 and Amendment3 9.3 Adequate bone marrow, liver, and renal function: a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent transfusions in preceding 2 weeks): -Absolute neutrophil count (ANC) greater than or equal to 1,000/mm3 -Platelet count greater than or equal to 75,000/mm3 -Hemoglobin greater than or equal to 8.0 g/dL b. Liver function: -Total bilirubin less than or equal to 1.5 x institutional ULN OR direct bilirubin less than or equal to ULN for subjects with total bilirubin levels greater than 1.5xULN -Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5x institutional ULN or less than or equal to 5x institutional ULN for subjects with liver metastases c. Renal function: Creatinine clearance (CrCl) greater than 30 mL/min calculated using the Cockcroft-Gault formula for adult subjects or the CKiD (Chronic Kidney Disease in Children) Schwartz formula for children and adolescent subjects (greater than or equal to 6 to less than 18 years of age) (Section 10.7) d. Phosphate: less than ULN within 14 days of treatment and prior to Cycle 1 Day 1 (medical management allowed), 2. Criterion modified per Amendment 1 2.1 Criterion modified per Amendment 2 2.2 Criterion modified per Amendment 3 2.3 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).Molecular Criteria for Broad Panel Cohort and Cholangiocarcinoma Expansion Cohort: *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. Molecular Criteria for Pediatric Cohort: *Subjects with any FGFR mutation*** (exclusive of FGFR valine gatekeeper and resistance alterations defined in the Exclusion Criteria) or any** FGFR gene fusions, or FGFR internal tandem duplication**** are eligible for enrolment in the Pediatric Cohort **FGFR Fusion Specifications: - 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 FGFRGENE 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) (Broad Panel Cohort only) -FGFR gene identifiers, canonical transcript identifiers, and kinase domain positions are provided, see Section 5.1., 3. Measurable disease according to RECIST v1.1 or RANO for primary brain tumors., 4. Criterion modified per Amendment 2 4.1 Criterion modified per Amendment 3 4.2 Subject must have received at least one prior line of systemic therapy in the advanced, unresectable, or metastatic setting; or is a child or adolescent subject with a newly-diagnosed solid tumor and no acceptable standard therapies., 5. Subject does not have standard of care options that have shown meani
Any potential subject who meets any of the following criteria will be excluded from participating in the study: 1. Criterion modified per Amendment 2 1.1 Criterion modified per Amendment 3 1.2 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 immunotherapy-related toxicity., 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. Criterion modified per Amendment 3 11.3 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 children and 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 planning to become pregnant while enrolled in this study or within 3 months after the last dose of drug., 19. Plans to father a child while enrolled in this study or within 3 months after the last dose of drug., 2. Criterion modified per Amendment 2 2.1 Criterion modified per Amendment 3 2.2 The known* presence of FGFR valine gatekeeper and resistance alterations. Mutations in the following positions: FGFR1 V561; FGFR2 V564; FGFR3 V555; FGFR4 V550; FGFR1 N546; FGFR2 N549; FGFR3 N540 and FGFR4 N535. * Observation of a gatekeeper/resistance alteration in the local or central report. If the local test does not screen for all four FGFRs, eg FGFR4, the local report remains evaluable for molecular screening., 20. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Examples include ongoing active infection requiring systemic therapy and uncont
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method