Gilteritinib for the Treatment of ALK NSCLC

Phase I Study of Gilteritinib for ALK Positive Non-Small Cell Lung Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Biopsy; Drug: Gilteritinib; Procedure: Echocardiography

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Not yet recruiting
      • Cedars-Sinai Medical Center
      • Principal Investigator: Kamya Sankar, MD
      • Contact: Maria Tarallo; Phone Number: 310-423-1840; Email: Maria.Tarallo@cshs.org
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Not yet recruiting
      • Georgetown University
      • Principal Investigator: Joshua Reuss, MD
      • Contact: Mathew Caffet; Phone Number: 202-444-2223; Email: Mc2731@georgetown.edu
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Comprehensive Cancer Center
      • Principal Investigator: Angel Qin
      • Contact: Angel Qin; Phone Number: 734-647-8902; Email: qina@med.umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

  • If the patient is symptomatic, there is vasogenic edema, and/or there is midline shift, the patient will need to undergo treatment for these brain metastases and meet exclusion criteria #4 exception to treated brain metastases prior to enrollment. A new MRI brain is NOT required in this situation
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Procedure: Biopsy; Undergo tissue biopsy; Other Names: Bx; BIOPSY_TYPE; Drug: Gilteritinib; Given PO; Other Names: ASP2215; ASP-2215; Procedure: Echocardiography; Undergo echocardiography; Other Names: EC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor response	Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Best responses including complete response, partial response, stable disease and progressive disease will be determined by independent radiology assessment.	Up to 2 years after last dose of gilteritinib
Progression-free survival (PFS)	Determined by RECIST v 1.1.	From start of treatment to time of progression, assessed up to 2 years after last dose of gilteritinib
Overall survival (OS)	Median OS and associated 95% confidence intervals will be assessed and reported using the Kaplan-Meier method.	Cycle 1 day 1 of study start to date of death from any cause, assessed up to 2 years from last dose of gilteritinib

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Angel Qin, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: January 13, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Actual): January 26, 2024

Study Record Updates

• Last Update Posted (Actual): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 15, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; gilteritinib
• Other Study ID Numbers: UMCC 2023.047 (Other Identifier: University of Michigan Comprehensive Cancer Center); NCI-2023-10639 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes