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.Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 21.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 100000004864
- Registration Number
- EUCTR2019-002113-19-DK
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 336
1. Criterion modified per Amendment 3
1.1 =6 years of age
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 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) (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 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. Criterion modified per Amendment 3
8.1 For adults (=18 years of age), ECOG performance status Grade 0 or 1 (Section 10.5)
For children and adolescents (=6 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. Criterion modified per Amendment 1
9.1 Criterion modified per Amendment 2
9.2 Criterion modified per Amendment 3
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) = 1,000/mm3
-Platelet count = 75,000/mm3
-Hemoglobin = 8.0 g/dL
b. Liver function:
-Total bilirubin =1.5 x instit
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.
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 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 Criterion modified per Amendment 3
3.3 For NSCLC subjects only - pathogenic somatic mutations in EGFR* or BRAF V600E, KRAS 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.
3.4 For colorectal subjects only – pathogenic somatic mutations in BRAF, KRAS, NRAS and PIK3CA.
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 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. 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/decu
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