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 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

1. 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.
2. 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.
3. Participant must have at least one prior line of ALK inhibitor-based therapy and meet one of the following criteria:
4. 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.
5. Participant received lorlatinib as one of the prior ALK inhibitor regimens.
6. 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.
7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of =
8. - Participant must have had progression or recurrence of NSCLC during or following receipt of the most recent therapy.
9. Female participant is not pregnant and at least 1 of the following conditions apply:
10. Not a woman of childbearing potential (WOCBP).
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. Male participant must not donate sperm during the treatment period and for 120 days after final study intervention administration.
17. Participant must meet the criteria as indicated on the clinical laboratory tests.
18. Participant agrees not to participate in another interventional study while receiving study intervention in the present study/participating in the present study.

Treatment Sites in Georgia