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 gene alterations.MedDRA version: 21.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002113-19-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 310
Please refer to protocol section 5.1
1. >=12 years of age
2. crterion ameded per Amendment1 and per Amendment2
2.1 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).
*Locally performed or commercial testing results 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 lab.
**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 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)
-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. Progression of disease, defined as any progression that requires a change in treatment, prior to full study screening
7. Toxicities from anticancer therapies must be resolved to baseline levels or to Grade 1 or less except for alopecia, peripheral neuropathy,
8. For adults (=18 years of age), ECOG performance status Grade 0 or 1 (Section 10.5) For adolescents (=12 to <16 years of age), Lansky Score of =80 (Section 10.6). For adolescents (=16 to <18 years of age), Karnofsky Score of =80
(Section 10.6).
9. Adequate bone marrow, liver, and renal function:
a. Bone marrow function (without the support of cytokines or erythropoiesis-stimulating agent in preceding 2 weeks): -Asolute neutrophil count (ANC) >=1,000/mm3 -Patelet count >=75,000/mm3 -Hemoglobin >=8.0 g/dL
b. Liver function: -Total bilirubin =1.5 x institutional ULN OR direct bilirubin =ULN for subjects with total bilirubin levels >1.5xULN -Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5x nstitutional ULN or =5x institutional ULN for subjects with liver metastases
c. Renal function: Creatinine clearance >30 mL/min/1,73m2 either directly measured via 24-hour urine collection or calculated using the Cockcroft- Gault formula for adult subjects or the CKiD (Chronic Kidney
Disease in Children)Schwartz formula for adolescent subjects (Section 10.7)
d. Phosphate: 10. Must sign an ICF. For adolescent subjects, parent(s) (preferably both if available) (or their legally acceptable representative) must sign an ICF . Assent is also required of adolescent subjects as described in Informed Consent Process in Section 10.3,
11. A female of childbearing potential must have a negative pregnanc
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) up to 30 days before the first dose of erdafitinib. Has had prior mAb therapy or immunotherapy within 30 days before the first dose of erdafitinib and/or has an ongoing Grade =2 immunotherapyrelated toxicity
2. 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. For NSCLC subjects only - pathogenic somatic mutations or gene fusions in the following genes: EGFR, BRAF v600EALK, ROS1, and NTRK and BRAT V600E
*Assessment of these genes may be performed per institutional standard and do not have to be assessed via NGS.
4. Histologic demonstration of transitional cell 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. Received prior selective FGFR 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. 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 as confirmed by triplicate assessment at screening (Fridericia; QTc >480 milliseconds; for adoloescent 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. 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 test and subjects with inactive hepatitis B with positive HBsAg antibody 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. Palliative radiation to the target lesionwithin 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.
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 confo
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