A Phase 1b Study of Gilteritinib in Participants with Locally Advanced or Metastatic NSCLC with ALK Rearrangement After Prior Treatment with an ALK Inhibitor
Study Description
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
confirmed locally advanced or metastatic NSCLC with a documented ALK rearrangement and is not amenable to curative intent treatment.
willing to submit, prior to enrollment, a fresh tumor tissue sample. If it is not medically feasible enrollment into the study should be confirmed with medical monitor. In this case, an archival tumor tissue sample must be provided.
At least one prior line of ALK inhibitor-based therapy and meet one of the following criteria:
Received alectinib as the only prior ALK inhibitor regimen. Eligible if chemotherapy was received in the neoadjuvant or adjuvant setting, and relapse or disease progressed after 12 months from completion of the treatment.
Received lorlatinib as one of the prior ALK inhibitor regimens.
Measurable disease according to RECIST v 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
ECOG performance status of less than or equal to 2
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 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.
Must not be breastfeeding or lactating
Must not donate ova starting at the first administration of study intervention
Must agree to use contraception with partner(s) of childbearing potential
Must agree to remain abstinent or use a condom with pregnant partner(s)Male participant must not donate sperm during the treatment period and for 120 days after final study intervention administration.
Must meet the criteria as indicated on the clinical laboratory tests
Agree not to participate in another interventional study while receiving study intervention
Has known oncogenic driver alterations other than ALK rearrangement.
Has symptomatic CNS metastases or has leptomeningeal metastasis.
Has history of malignancy other than NSCLC within 2 years before screening
Had major surgery within 4 weeks prior to first dose of study intervention
Has ongoing clinically significant toxicity associated with prior anti-cancer treatment.
Has/had febrile illness or symptomatic, viral, bacterial or fungal infection within 28 days prior to first dose
History of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease or a family history of long QT syndrome
History of a cerebral vascular event unstable angina, MI or cardiac symptoms within 6 months prior to the first dose of study intervention
History of interstitial pneumonia.
Had completed target therapy, radiotherapy, chemotherapy, biologics and/or immunotherapy within 14 days prior to first dose
Requires treatment with strong inducers of cytochrome P450 (CYP) 3A.
Requires treatment with concomitant drugs that target serotonin 5HT1 or 5HT2B receptors or sigma nonspecific receptor
Received any investigational therapy within 14 days or 5 half-lives prior to screening
Mean Fridericia-corrected QT interval (QTcF) of > 450 msec
Active HBV infection or active HCV infection
HBsAg-positivity and/or anti-HBV core antibody-positivity
Has been curatively treated for HCV infection is permitted if he/she has documented sustained virologic response of 12 weeks
Known history of HIV infection with AIDS-related complications
ECHO or MUGA at screening revealing left ventricular ejection fraction < 45%.
Any condition that makes the participant unsuitable for study participation.
Known or suspected hypersensitivity to gilteritinib or any components of the formulation used.
