A Phase 1b Study of Gilteritinib in Participants With Locally Advanced or Metastatic NSCLC With ALK Rearrangement After Prior Treatment With an ALK Inhibitor

Plain English Summary

A Study of Gilteritinib in Adults With Advanced ALK-positive Non-small Cell Lung Cancer (NSCLC) is a Phase 1 clinical trial sponsored by Astellas Pharma Global Development, Inc. studying Non-small Cell Lung Cancer (NSCLC), Anaplastic Lymphoma Kinase (ALK) Positive. This trial tests the drug gilteritinib in adults with a specific type of advanced non-small cell lung cancer (NSCLC) that has spread and no longer responds to ALK inhibitor drugs. It is for patients with ALK-positive NSCLC who have previously been treated with ALK inhibitors like alectinib or lorlatinib and whose cancer has progressed. Participants will take gilteritinib tablets daily. The study will monitor for side effects and how well the drug works. Alternative treatments may include other chemotherapy or targeted therapies, depending on the patient's specific situation and prior treatments. The trial aims to enroll 40 participants.

Official Summary

Genes give your body instructions on how to make proteins. Proteins are needed to keep the body working properly. Many types of cancer are caused by changes in certain genes, making them faulty. Some people with non small cell lung cancer (NSCLC) have a faulty ALK gene. ALK stands for anaplastic lymphoma kinase. People with NSCLC who have the faulty ALK gene are called ALK-positive. ALK inhibitors are an approved treatment for people with ALK positive NSCLC. Some people stop responding to treatment with ALK inhibitors over time due to more changes happening in their faulty ALK gene, so there is an unmet medical need. Gilteritinib is an approved treatment for people with acute myeloid leukemia (AML) with the faulty FLT3 gene who haven't responded to previous treatment, or their cancer came back after previous treatment. Gilteritinib also blocks changes in the ALK gene which could help people with ALK-positive NSCLC. A study needs to be done with gilteritinib in people with ALK-positive NSCLC. The main aim of the study is to check the safety of gilteritinib in people with ALK-positive NSCLC and if they tolerate gilteritinib. People in this study will be adults with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC). Locally advanced means the cancer has spread to nearby tissue. Metastatic means the cancer has spread to other parts of the body. They have stopped responding to treatment with ALK inhibitors, including alectinib or lorlatinib, over time. The key reasons people cannot take part are if they have symptomatic cancers in the brain or nervous system, their cancer has spread to the thin tissue that covers the brain and spinal cord (leptomengingeal metastasis), have recently had or planning to have major surgery, have certain heart conditions, or have recently had an infection, a stroke or mini-stroke. People in the study will take tablets of gilteritinib once a day in a 28-day cycle. They may be given up to 2 different doses of gil

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with non-small cell lung cancer (NSCLC) that has spread and has an ALK gene change. Patients must have previously been treated with an ALK inhibitor (like alectinib or lorlatinib) and their cancer has worsened. Individuals with active brain or spinal cord spread of cancer, certain heart conditions, or recent major surgery or infections cannot join. Patients must be able to provide a recent tumor tissue sample or an archival one if a fresh sample isn't possible. This trial is studying Non-small Cell Lung Cancer (NSCLC), Anaplastic Lymphoma Kinase (ALK) Positive, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure the safety and tolerability of gilteritinib, meaning how well patients can take the drug without severe side effects and if it's safe to use in this population. The specific primary outcome measures are: Number of Participants with Dose Limiting Toxicity (DLT) (Up to 28 Days); Number of participants with Adverse Events (AEs) (Up to approximately 53 Months); Number of participants with Serious Adverse Events (SAEs) (Up to approximately 53 Months); Number of participants with laboratory value abnormalities and/or adverse events (AEs) (Up to approximately 53 Months); Number of participants with vital sign abnormalities and/or adverse events (AEs) (Up to approximately 53 Months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses an unmet need for patients with ALK-positive lung cancer who have stopped responding to existing ALK inhibitor treatments, exploring a new option for this group. This research targets Non-small Cell Lung Cancer (NSCLC), Anaplastic Lymphoma Kinase (ALK) Positive, where improved treatment options are needed.

Investor Insight

This trial investigates gilteritinib, an approved drug for AML, in a new indication for NSCLC, potentially expanding its market and offering a new treatment avenue if successful. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if gilteritinib is a suitable option for you, considering your specific cancer and treatment history. Be prepared to provide tumor tissue samples for testing. Participation involves taking daily medication and attending regular study visits for monitoring. This trial is currently recruiting participants. The trial is being conducted at 10 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 40 participants

Interventions

• DRUG: gilteritinib — Oral

Primary Outcomes

• Number of Participants with Dose Limiting Toxicity (DLT) (Up to 28 Days)
• Number of participants with Adverse Events (AEs) (Up to approximately 53 Months)
• Number of participants with Serious Adverse Events (SAEs) (Up to approximately 53 Months)
• Number of participants with laboratory value abnormalities and/or adverse events (AEs) (Up to approximately 53 Months)
• Number of participants with vital sign abnormalities and/or adverse events (AEs) (Up to approximately 53 Months)

Secondary Outcomes

• Objective Response Rate (ORR) (Up to approximately 53 Months)
• Duration of Response (DOR) (Up to approximately 53 Months)
• Disease Control Rate (DCR) (Up to approximately 53 Months)
• Progression Free Survival (PFS) (Up to approximately 53 Months)
• Intracranial Objective Response Rate (IC-ORR) (Up to approximately 53 Months)

Full Eligibility Criteria

Inclusion Criteria:

* Participant has histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with a documented anaplastic lymphoma kinase (ALK) rearrangement and is not amenable to curative intent treatment.
* Participant is willing to submit, prior to enrollment, a fresh tumor tissue sample that was collected after completion of the most recent anti-cancer treatment and before the first dose of study intervention. If it is not medically feasible for a participant to provide a fresh tumor tissue sample, enrollment into the study should be confirmed with the Astellas medical monitor. In this case, an archival tumor tissue sample must be provided.
* Participant must have at least one prior line of ALK inhibitor-based therapy and meet one of the following criteria:

  * Participant received alectinib as the only prior ALK inhibitor regimen. Participant is ineligible or unable to tolerate approved and available second-line therapy, or is determined to potentially benefit from gilteritinib in this setting. Participant is eligible if chemotherapy was received in the neoadjuvant or adjuvant setting, and relapse or disease progressed after 12 months from completion of the treatment.
  * Participant received lorlatinib as one of the prior ALK inhibitor regimens.
* Participant has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
* Participant must have had progression or recurrence of NSCLC during or following receipt of the most recent therapy.
* Female participant is not pregnant and at least one of the following conditions apply:

  * Not a woman of childbearing potential (WOCBP).
  * WOCBP who has a negative urine or serum pregnancy test within 7 days prior to the first dose of study intervention and agrees to follow the contraceptive guidance from the time of informed consent through at least 180 days after final study intervention administration.
* Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 60 days after final study intervention administration.
* Female participant must not donate ova starting at the first administration of study intervention and throughout the investigational period and for 180 days after final study intervention administration.
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 120 days after final study intervention administration.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 120 days after final study intervention administration.
* Male participant must not donate sperm during the treatment period and for 120 days after final study intervention administration.
* Participant must meet the criteria as indicated on the clinical laboratory tests.
* Participant agrees not to participate in another interventional study while receiving study intervention in the present study/participating in the present study.

Exclusion Criteria:

* Participant has known oncogenic driver alterations other than ALK rearrangement.
* Participant has symptomatic central nervous system (CNS) metastases or has leptomeningeal metastasis.
* Participant has a history of malignancy other than NSCLC within 2 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix or malignancy considered cured with minimal risk of recurrence).
* Participant had major surgery (e.g., requiring general anesthesia) within 4 weeks prior to first dose of study intervention, or will not have fully recovered from surgery, or has surgery planned during the study treatment.
* Participant has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior anti-cancer treatment.
* Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 28 days prior to first dose of study intervention.
* Participant has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease or a family history of long QT syndrome.
* Participant has a history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study intervention.
* Participant has a his

Trial Locations

• OSF Health Care, Peoria, Illinois, United States
• University of Michigan Health Systems, Ann Arbor, Michigan, United States
• Washington University School of Medicine, St Louis, Missouri, United States
• Hackensack University Medical Center, Hackensack, New Jersey, United States
• UT Southwestern Medical Center at Dallas, Dallas, Texas, United States
• Virginia Cancer Specialists PC, Fairfax, Virginia, United States
• Site ES34017, Barcelona, Spain
• Site ES34006, Madrid, Spain
• Site ES34011, Madrid, Spain
• Site ES34008, Málaga, Spain

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer (NSCLC)
• Anaplastic Lymphoma Kinase (ALK) Positive NSCLC
• ALK Inhibitor Resistance
• Metastatic Lung Cancer
• Advanced Lung Cancer
• Targeted Cancer Therapy
• Oncology
• Genomic Alterations in Cancer
• Acute Myeloid Leukemia (AML) - related to gilteritinib's existing approval
• Cancer Treatment Resistance

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