Testing the Anti-cancer Drug Erdafitinib for Brain Cancers That Have Returned or Progressed Following Treatment

Inclusion Criteria:

• Patient must be >= 18 years of age

• Patient must have histologically confirmed IDH-WT gliomas (grade 2-4) as per WorldHealth Organization (WHO) 2016 or 2021 classification

• Tumor tissue should be positive for FGFR-TACC gene fusion as per any local nextgeneration sequencing (NGS) (Clinical Laboratory Improvement Act [CLIA]-approved)assay described in background section

• The disease should be recurrent or progressive glioma after initial anti-tumortreatment with at least 1 line of treatment including surgical resection, radiationtherapy and/or chemotherapy

• For patients with WHO grade 3 or 4 glioma and progressive disease < 12 weeks aftercompletion of chemoradiotherapy, progression can be defined by the following set ofcriteria:

• New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line)

• If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. i.e., > 70% tumor cell nuclei in areas), high orprogressive increase in Ki-67 proliferation index compared with prior biopsy,or evidence for histologic progression or increased anaplasia in tumor)

• For patients with WHO grade 3 or 4 glioma and progressive disease >= 12 weeks aftercompletion of chemoradiotherapy, progression can be defined by the following set ofcriteria:

• New contrast-enhancing lesion outside of radiation field on decreasing, stable,or increasing doses of corticosteroids

• Increase by >= 25% in the sum of the products of perpendicular diametersbetween the first post-radiotherapy scan, or a subsequent scan with smallertumor size, and the scan at 12 weeks or later on stable or increasing doses ofcorticosteroids

• For patients receiving antiangiogenic therapy, significant increase in T2/fluidattenuated inversion recovery (FLAIR) non-enhancing lesion may also beconsidered progressive disease. The increased T2/FLAIR must have occurred withthe patient on stable or increasing doses of corticosteroids compared withbaseline scan or best response after initiation of therapy and not be a resultof comorbid events (e.g., effects of radiation therapy, demyelination, ischemicinjury, infection, seizures, postoperative changes, or other treatment effects)

• For patients with WHO grade 2 glioma progression is defined by any one of thefollowing:

• Development of new lesions or increase of enhancement (radiological evidence ofmalignant transformation)

• A 25% increase of the T2 or FLAIR non-enhancing lesion on stable or increasingdoses of corticosteroids compared with baseline scan or best response afterinitiation of therapy, not attributable to radiation effect or to comorbidevents

• There must be measurable disease (enhancing or non-enhancing as per ResponseAssessment in Neuro-Oncology [RANO] or RANO-low-grade glioma [LGG] criteria), asevaluated on pre-treatment MRI

• Patient understands the procedures and investigational nature of the study drug andagrees to comply with study requirements by providing written informed consent

• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (or Karnofsky >= 60%)

• Absolute neutrophil count >= 1000/uL

• Hemoglobin > 8 g/dL (Patients are allowed to be transfused to this level)

• Platelets >= 100 x 10^9/L

• Serum total bilirubin =< 1.5 x upper limit of normal (ULN), unless considered due toGilbert's disease or disease involvement following approval by the medical monitor

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN

• Creatinine clearance > 30 mL/min (patients with mild or moderate renal impairment)based on the Cockroft-Gault glomerular filtration rate (GFR) estimation

• Patient must have normal serum phosphate level as per local laboratory parameters. (Medical management allowed)

• Patient must be recovered from any clinically relevant toxic effects of any priorsurgery, radiotherapy, or chemotherapy treatment with temozolomide

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviraltherapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treatedand cured. For patients with HCV infection who are currently on treatment, they areeligible if they have an undetectable HCV viral load

• Patients should be New York Heart Association Functional Classification class 2B orbetter

• The effects of erdafitinib on the developing human fetus are unknown. For thisreason and because FGFR inhibitors are known to be teratogenic, women ofchild-bearing potential and men must agree to use adequate contraception (hormonalor barrier method of birth control; abstinence) prior to study entry, for theduration of study participation, and one month after completion of erdafitinibadministration. Should a woman become pregnant or suspect she is pregnant while sheor her partner is participating in this study, she should inform her treatingphysician immediately. Men treated or enrolled on this protocol must also agree touse adequate contraception prior to the study, for the duration of studyparticipation, and one month after completion of erdafitinib administration

• Ability to understand and the willingness to sign a written informed consentdocument. Legally authorized representatives may sign and give informed consent onbehalf of study participants

Exclusion Criteria:

• Patients who are receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to erdafitinib

• Patients requiring any medications or substances that are moderate CYP2C9 inducersand strong CYP3A4 inducers are ineligible. Because the lists of these agents areconstantly changing, it is important to regularly consult a frequently-updatedmedical reference. As part of the enrollment/informed consent procedures, thepatient will be counseled on the risk of interactions with other agents, and what todo if new medications need to be prescribed or if the patient is considering a newover-the-counter medicine or herbal product

• Patients with uncontrolled intercurrent illness

• Pregnant women are excluded from this study because erdafitinib is an FGFR inhibitoragent with the potential for teratogenic or abortifacient effects. Because there isan unknown but potential risk for adverse events in nursing infants secondary totreatment of the mother with erdafitinib, breastfeeding should be discontinued ifthe mother is treated with erdafitinib

• Current central serous retinopathy (CSR) or retinal pigment epithelial detachment ofany grade

• Corrected QT interval (QTc) prolongation as confirmed by electrocardiography (ECG)at screening (Fridericia; QTc > 480 milliseconds)

• Patients who have previously received FGFR inhibitors