Testing JNJ-42756493 (Erdafitinib) as Potentially Targeting Treatment in Cancers With FGFR Amplifications (MATCH-Subprotocol K1)

NCT ID: NCT06308822

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-20
• Study Completion Date: 2025-12-31

Brief Summary

This phase II MATCH treatment trial tests how well JNJ-42756493 (erdafitinib) works in treating patients with tumors that have more copies of the FGFR gene than is normal (amplification). Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive erdafitinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and magnetic resonance imaging (MRI) throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for 1 year.

THE MATCH SCREENING TRIAL:

Please see NCT02465060 for information on the MATCH Screening Protocol and applicable documents.

Conditions

Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (erdafitinib)

Patients receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial.

Group Type: EXPERIMENTAL

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo tumor biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT

Erdafitinib

Intervention Type: DRUG

Given PO

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Interventions

Biopsy Procedure

Undergo tumor biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Computed Tomography

Undergo CT

Intervention Type: PROCEDURE

Erdafitinib

Given PO

Intervention Type: DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Other Intervention Names

Biopsy; BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected; Specimen Collection; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; tomography; Balversa; JNJ 42756493; JNJ-42756493; JNJ42756493; Magnetic Resonance; Magnetic Resonance Imaging (MRI); Magnetic resonance imaging (procedure); Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI; MRI Scan; MRIs; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Structural MRI

Eligibility Criteria

Inclusion Criteria

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol.
• Patients must fulfill all eligibility criteria outlined in MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7).
• Patients must have FGFR Amplification as determined via the MATCH Master Protocol.
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block).
• Patients must not have known hypersensitivity to JNJ-42756493 (erdafitinib) or compounds of similar chemical or biologic composition.
• Patients with current evidence of corneal or retinal disorder/keratopathy are excluded.
• Patients must not be currently using medications that can elevate serum phosphorous and/or calcium levels.

• Medications that increase serum calcium should be avoided. Over the counter calcium supplements, antacids that contain calcium (Tums) and vitamin D supplements (cholecalciferol and ergocalciferol) should be avoided. Prescription medications including lithium, hydrochlorothiazide and chlorthalidone must be used with caution.
• Medications that increase serum phosphate should be avoided. Over the counter laxatives that contain phosphate such as Fleets oral or Fleets enema and Miralax should be avoided.
• Patients with a history of hyperphosphatemia will be excluded.
• Patients may not have received strong inhibitors or potent inducers of CYP3A within 2 weeks before the first dose of study treatment. Patients with inability to discontinue treatment with a strong CYP3A4 and/or CYP2C9 inhibitor or inducer prior to start of treatment are excluded.
• Patients who have previously received treatment with a FGFR-targeted inhibitor are excluded. Such inhibitors include AZD4547, BGJ398, BAY1163877 and LY2874455). Prior non-selective FGFR inhibitor treatment (e.g. Pazopanib, dovitinib, ponatinib, brivanib, lucitanib, lenvatinib) are allowed.
• Patients must not have any history of or current evidence of renal or endocrine alterations of calcium/phosphate homeostasis, or history of or current evidence of extensive tissue calcification (by evaluation of the clinician), including but not limited to, the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic vascular calcification per investigators' judgment.
• Patients with transitional cell carcinoma of the bladder and /or urothelial tract are not eligible. These patients are encouraged to enroll in the ongoing disease-specific studies.
• Patients with impaired renal function (glomerular filtration rate [GFR] < 60 mL/min) are excluded. GFR should be assessed by direct measurement (i.e., creatinine clearance or ethyldediaminetetraacetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula).
• Patients with persistent phosphate level > upper limit of normal (ULN) during screening (within 14 days of treatment and prior to cycle 1 day 1) and despite medical management are excluded.
• Patients with a history of or current uncontrolled cardiovascular disease as stated below are excluded:

• Unstable angina, myocardial infarction, or known congestive heart failure class II-IV within the preceding 12 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months, pulmonary embolism within the preceding 2 months.
• Any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy.
• Patients with impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions are excluded.
• Female subjects (of child-bearing potential and sexually active) must use medically acceptable methods of birth control (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of the study, and for 4 months after the last intake of study drug. Male subjects (with a partner of child-bearing potential) must use a condom with spermicide when sexually active and must not donate sperm from the first dose of study drug until 5 months after the last dose of study drug.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alain C Mita

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

NCI-2024-01151

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAY131-K1

Identifier Type: OTHER

Identifier Source: secondary_id

EAY131-K1

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-01151

Identifier Type: -

Identifier Source: org_study_id