Gilteritinib for the Treatment of ALK NSCLC

NCT06225427 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: UMCC 2023.047NCI-2023-10639
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Safety will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

  Up to 30 days after last dose of gilteritinib

• Dose-limiting toxicities (DLT)

  Toxicities will be assessed by CTCAE v 5.0. DLT's will be defined as \>= grade 4 hematologic toxicities, \>= grade 3 febrile neutropenia, \>= grade 3 non-hematologic toxicities, and posterior reversible encephalopathy syndrome of any grade. Toxicity will be quantified by reporting the proportion of patients who experience a DLT at the identified maximum tolerated dose and by reporting a 95% confidence interval for this proportion.

  Cycle 1 day 1 up to cycle 2 day 1 (each cycle is 21 days)

Secondary Outcomes (3)

• Anti-tumor response

  Up to 2 years after last dose of gilteritinib

• Progression-free survival (PFS)

  From start of treatment to time of progression, assessed up to 2 years after last dose of gilteritinib

• Overall survival (OS)

  Cycle 1 day 1 of study start to date of death from any cause, assessed up to 2 years from last dose of gilteritinib

Study Arms (1)

Treatment (gilteritinib)

EXPERIMENTAL

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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Drug: Gilteritinib; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration

Interventions

Biopsy PROCEDURE

Undergo tissue biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (gilteritinib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (gilteritinib)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (gilteritinib)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (gilteritinib)

Gilteritinib DRUG

Given PO

Also known as: ASP-2215, ASP2215

Treatment (gilteritinib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: 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

Treatment (gilteritinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (gilteritinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (3)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

NOT YET RECRUITING

Georgetown University

Washington D.C., District of Columbia, 20007, United States

NOT YET RECRUITING

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Biopsy; Specimen Handling; gilteritinib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Angel Qin

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2024
• First Posted: January 26, 2024
• Study Start: July 25, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)