A Study of Gilteritinib in Adults With Advanced ALK-positive Non-small Cell Lung Cancer (NSCLC)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAstellas Pharma Global Development, Inc.
About this trial
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 gilteritinib. People in the study will start on the lower dose but can eventually switch to the higher dose if they tolerate the lower dose and meet the safety checks.
Whilst taking gilteritinib, people will have regular scans of their tumors. People will continue taking gilteritinib until their cancer gets worse, they have medical problems from gilteritinib that they can't tolerate, they ask to stop taking gilteritinib, they start other cancer treatment or, sadly pass away. People will visit the clinic about 7 days and then 30 days after they stop taking gilteritinib. They will be asked about any medical problems and will have a safety check. After this, people who stopped taking gilteritinib, but their cancer hadn't become worse, will continue to have regular scans of their tumors. If their cancer does get worse, they will no longer have scans of their tumors. After finishing gilteritinib, people will be phoned every 12 weeks to check on their health. People will be in the study for up to 4 years, depending on how they respond to gilteritinib.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 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.
Disqualifiers
Participant has known oncogenic driver alterations other than ALK rearrangement.
Participant has symptomatic central nervous system (CNS) metastases or 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.
Trial design
Design model
Single group
Treatments tested in this trial
gilteritinib
DrugOral
Treatment groups
40 Participants
are divided into 1 treatment groupGroup A: gilteritinibExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Number of Participants with Dose Limiting Toxicity (DLT)
A Dose Limiting Toxicity is defined as any event meeting the DLT criteria occurring within 28 days of first dose.
Time frame
Up to 28 Days2
Number of participants with Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame
Up to approximately 53 Months3
Number of participants with Serious Adverse Events (SAEs)
An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation to hospitalization, results in persistent or significant disability/incapacity, results in congenital anomaly or birth defect, or other medically important event.
Time frame
Up to approximately 53 Months4
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Time frame
Up to approximately 53 MonthsSecondary outcomes
1
Objective Response Rate (ORR)
ORR is defined as the proportion of participants whose best overall response is rated as confirmed Confirmed Response (CR) or Partial Response (PR) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1.
Time frame
Up to approximately 53 Months2
Duration of Response (DOR)
DOR is defined as the time from the date of first documented response (CR or PR that is subsequently confirmed) to the date of first documented PD as assessed by investigator based on RECIST v 1.1. or death due to any cause, whichever occurs first.
Time frame
Up to approximately 53 Months3
Disease Control Rate (DCR)
DCR is defined as the proportion of participants whose best overall response is rated as confirmed CR, PR or stable disease as assessed by investigator based on RECIST v1.1.
Time frame
Up to approximately 53 Months4
Progression Free Survival (PFS)
PFS is defined as the time from the date of first dose of study intervention until the date of first documented progressive disease (PD) as assessed by investigator based on RECIST v 1.1. or death due to any cause, whichever occurs first.
Time frame
Up to approximately 53 MonthsSponsors and contacts
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Source ClinicalTrials.gov