Gilteritinib for the Treatment of ALK NSCLC

NCT ID: NCT06225427

Last Updated: 2025-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-25

Study Completion Date

2027-05-31

Brief Summary

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This phase I trial is studying the safety, side effects, and best dose of gilteritinib in treating patients with stage IV ALK positive non-small cell lung cancer (NSCLC) who have progressed on other treatments. While there are many approved targeted drugs for ALK NSCLC, resistance to these drugs frequently occur. Giltertinib is a drug that is already FDA approved for the treatment of a specific type of leukemia. However, studies using ALK positive lung cancer cells demonstrate activity of gilteritinib against these resistant cells. Therefore, in this clinical trial, the investigators plan to study the effect of giltertinib in patients with ALK NSCLC.

Detailed Description

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Conditions

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Lung Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (gilteritinib)

Patients receive gilteritinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography at screening and blood sample collection, CT scan and MRI at screening and on study. Additionally, patients may undergo a tumor biopsy pre-treatment and at end of treatment.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo tissue biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Echocardiography

Intervention Type PROCEDURE

Undergo echocardiography

Gilteritinib

Intervention Type DRUG

Given PO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Biopsy

Undergo tissue biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Echocardiography

Undergo echocardiography

Intervention Type PROCEDURE

Gilteritinib

Given PO

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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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 CT CT Scan tomography EC ASP-2215 ASP2215 Magnetic Resonance 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

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Inclusion Criteria

* Stage IV (American Joint Committee on Cancer \[AJCC\] 8th edition) non-small cell lung cancer with an oncogenic ALK fusion
* Histologies include adenocarcinoma, squamous cell carcinoma, adenosquamous adenocarcinoma, and NSCLC NOS (not otherwise specified)
* The presence of an oncogenic ALK fusion established from any Clinical Laboratory Improvement Act (CLIA) certified laboratory
* The patient must belong to one of the following treatment cohorts.

* Cohort 1: Prior 1st generation ALK tyrosine kinase inhibitor (TKI) (crizotinib) and/or prior 2nd generation TKI (ceritinib, brigatinib, alectinib) and/or lorlatinib
* Cohort 2: Prior 1st generation ALK TKI (crizotinib) and/or prior 2nd generation TKI (ceritinib, brigatinib, alectinib) and/or lorlatinib, and platinum-doublet chemotherapy
* Cohort 3: Prior 1st generation ALK TK (crizotinib) and/or prior 2nd generation TKI (ceritinib, brigatinib, alectinib) and/or lorlatinib, platinum-doublet chemotherapy, and any other number of antineoplastic agents (including immunotherapy, standard or investigational)
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Absolute neutrophil count (ANC) ≥ 1500/mcL
* Platelets ≥ 100,000/mcL
* Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
* Measured or calculated creatinine clearance (CrCl) ≥ 50mL/min (calculated per Cockcroft-Gault formula)
* Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) (per institutional guidelines) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
* Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
* Albumin ≥ 2.5g/dL
* Female subject of childbearing potential should have a negative serum pregnancy test within 21 days of enrollment prior to receiving the first dose of study medication
* Female subjects of childbearing potential must be willing to use a highly effective method of contraception for the course of the study, through 180 days after the last dose of study medication. Note: Abstinence is acceptable, if patient documents that this is their usual lifestyle or preferred contraception method
* Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 4 months after the last dose of study therapy. Note: Abstinence is acceptable, if patient documents that this is their usual lifestyle or preferred contraception method
* Ability to swallow pills orally and per investigator's assessment, do not have any significant issues limiting absorption of drug
* Ability to understand and the willingness to sign a written informed consent
* Measurable disease per RECIST v1.1 criteria assessed per screening imaging
* If a cancerous lesion is easily and safely accessible, a pre-treatment biopsy of this lesion is strongly encouraged but NOT required prior to first dose of gilteritinib. Archival or fresh tissue biopsy may be used as long as it was obtained prior to cycle 1 day 1 (C1D1)
* At least 7 days must have elapsed since last anti-neoplastic TKI, chemotherapy, immunotherapy, or investigational agent prior to the first dose of gilteritinib

Exclusion Criteria

* Received palliative radiation within 7 days of enrollment
* Received prior therapy with a FLT3 inhibitor
* Has a concurrent active malignancy receiving interventional therapy unless it is the investigator's opinion that the concurrent active malignancy will NOT significantly impact the survival of the patient (i.e. early stage breast cancer or prostate cancer on hormonal therapy, basal cell carcinoma awaiting Moh's or other surgery and the respective interventional therapy does NOT interact or interfere with gilteritinib.
* Has known active and symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.

* Subjects with previously treated brain metastases may participate provided they are stable (clinically asymptomatic, and ≥ 2 weeks since completion of treatment) and are not using steroids for at least 7 days prior to enrollment. A repeat MRI brain is not necessary to document stability
* Patients with carcinomatous meningitis are excluded regardless of clinical stability
* If a patient is found to have new/enlarging brain metastases on the screening MRI, the patient may be monitored closely and radiation could be delayed if the patient has no symptoms, there is no vasogenic edema, and there is no evidence of midline shift.

* Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment
* Has Child-Pugh class C cirrhosis from any cause
* Mean triplicate screening electrocardiogram (EKG) corrected QT (QTc) \> 480 ms
* Grade 3 or 4 NYHA (New York Heart Association) congestive heart failure, unless screening echocardiogram obtained prior to enrollment showed a LVEF (left ventricular ejection fraction) ≥ 45%
* Surgery within 4 weeks prior to first study dose
* Requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A
* Requires treatment with concomitant drugs that are strong inhibitors or inducers of P-glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the patient
* Requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor, with the exception of drugs that are considered absolutely essential for the care of the patient
* Active/untreated hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; patients with treated HBV and HCV are allowed as long as they meet the AST/ALT and bilirubin criteria
* Known hypersensitivity to gilteritinib or any of the excipients
* Active and clinically significant pancreatitis
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Michigan Rogel Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Angel Qin

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Rogel Cancer Center

Locations

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Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

Georgetown University

Washington D.C., District of Columbia, United States

Site Status NOT_YET_RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Maria Tarallo

Role: primary

310-423-1840

Mathew Caffet

Role: primary

202-444-2223

Angel Qin

Role: primary

734-647-8902

Other Identifiers

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NCI-2023-10639

Identifier Type: REGISTRY

Identifier Source: secondary_id

UMCC 2023.047

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2023.047

Identifier Type: -

Identifier Source: org_study_id

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