The expanded Gilteritinib ALK trial is now open
ALK NSCLC Trial #2 (Sponsored by Astellas)
Phase 1 Clinical Trial NCT07140016 sponsored by Astellas Pharma Global Development
A Study of Gilteritinib in Adults with Advanced ALK-Positive Non-small Cell Lung Cancer (NSCLC)
This is the second Gilteritinib ALK NSCLC trial and is sponsored this time by the drug’s Japanese manufacturer Astellas Global Development, Inc., and intended for 20 total sites in the U.S., Europe, and Japan. At this writing two sites are open and recruiting patients:
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Virginia Cancer Specialists PC
Fairfax, Virginia, United States, 22031
https://clinicaltrials.gov/study/NCT07140016?term=gilteritinib%20nsclc&rank=2
See this online resource for updates on additional trial sites opening and for contact information.
This trial is for patients progressing on >1 prior ALK inhibitor with measurable, locally advanced or metastatic, ALK-positive non-small cell lung cancer who have experienced alectinib as their only prior ALK inhibitor regimen, or have received lorlatinib as one of their prior ALK inhibitor regimens.
Note that prior treatment eligibility criteria are different in Trial #2 from Gilteritinib Trial #1.
Prior to enrollment, participant must submit a fresh tumor tissue sample collected after completion of their last anti-cancer treatment, and before the first dose of trial-provided gilteritinib. If providing fresh tumor tissue is not medically feasible, then the Astellas medical monitor must provide consent for an archival tumor tissue sample to be provided.
The trial drug is gilteritinib (aka Xospata), which was approved by the FDA in 2018 for the blood cancer acute myeloid leukemia (AML). It has shown to have activity against ALK NSCLC in patient-derived models (mice with transplanted human cancer). Made by Astellas Pharma, gilteritinib is a multi-kinase inhibitor with activity against ALK, AXL, RET, ROS1, MET, NTRK, FLT3 and other kinases that have been shown to generate ALK-independent resistance mechanisms. The drug has also shown in-vivo (in mice) efficacy against certain compound ALK mutations that lorlatinib has not. The estimated enrollment is forty patients. Participants must be at least 18 years of age.
This phase Ib trial will study the safety, tolerability, and best dose of gilteritinib in treating patients with stage IV ALK NSCLC. Although already approved for leukemia (AML), ALK NSCLC is a solid tumor, and the safety and best dose of gilteritinib may be different than for leukemia. Thus, the need for a phase Ib trial for an already approved drug. As the primary purpose of the study is to understand the safety of gilteritinib in patients with previously treated ALK NSCLC, the starting dose is the already approved 120mg daily (three pills). People in the study will take tablets of gilteritinib once a day in a 28-day cycle, and may be given up to 2 different doses of gilteritinib. Participants will start on the approved dose
(120mg daily) but can eventually escalate to the higher dose (240mg) if they tolerate the lower dose and meet the safety and efficacy checks. Note that this is also different from Gilteritinib Trial #1, where there is not an option for dose escalation. Only a dosage decrease is allowed in the event of intolerance in Trial #1. The primary objective is to understand safety and tolerability. The secondary objective is to understand response based on imaging and duration of the response.
Patients must be able to travel to their preferred site. Each treatment cycle is 28-days. For the first cycle, patients are coming in Day 1, 4, 8, 9, and 15. For cycle 2, they must come in Day 1, Day 15. All other cycles only have one visit every 28 days. The required washout period from prior drug treatments is at least 14 days. Scans are performed every 8 weeks for the first year. Certain procedures may need to be covered by the patient’s insurance, so it is recommended that interested patients check that their chosen site is in-network, or that their insurance has out-of-network benefits.
For information on gilteritinib Trial #1 see ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT06225427?term=gilteritinib%20nsclc&rank=1
Astellas Pharma is a multinational pharmaceutical company with headquarters in Tokyo, Japan, and subsidiaries worldwide, including Astellas Pharma US in Northbrook, Illinois. Their international reach allows them to serve patients and contribute to healthcare systems across the globe. Established in 2005 through the merger of Yamanouchi Pharmaceutical and Fujisawa Pharmaceutical, the company embodies a rich heritage and history of innovation. Astellas concentrates its efforts on developing and delivering effective medications across various therapeutic areas including oncology, urology, immunology (transplantation), cardiology, and infectious disease. With a dedication to innovation, a diverse range of expertise, and a global reach, Astellas is well-positioned to continue developing life-saving and life-changing medications for patients worldwide. https://www.astellas.com/en.
This trial represents a unique clinical collaboration between an academic institution, an advocacy organization, and a pharmaceutical company. In February of 2022, the Katayama research laboratory in Japan published a paper entitled Gilteritinib Overcomes Lorlatinib Resistance in ALK-rearranged Cancer. https://www.nature.com/articles/s41467-021-21396-w This drew the attention of the ALK Positive Research Acceleration Committee (RAC), and two members of the committee subsequently connected via video with one of the authors, Dr. Ryohei Katayama, to discuss the research. In the fall of that year Dr. Angel Qin, clinical lead of the University of Michigan ALK Initiative, requested that ALK Positive approach Astellas Pharma Inc, the maker of gilteritinib, about donating the drug for a clinical trial in ALK NSCLC patients. RAC members contacted the company at several levels, were directed to the formal application site and process, and generated support from the patient advocacy team at Astellas. A few weeks after Dr. Qin filed the application, a positive response was provided by the Japanese headquarters of Astellas. Thus began a process of continuing collaboration between Astellas, University of Michigan, and ALK Positive. Inc., leading to the first trial’s approval by all parties and opening for recruitment in April 2024. Continuing lobbying on behalf of ALK NSCLC patients by Dr. Qin and Dr. Ken Culver, ALK Positive’s Director of Research and Clinical Affairs has persuaded Astellas Pharma to fully sponsor this second, much larger trial for ALK patients. This report is being disseminated worldwide to ALK positive patients and caregivers numbering over 4,000 via Facebook, and over 8,000 via email newsletter, further establishing ALK Positive, Inc.’s role as an enabler of collaborative cancer treatment development. https://www.alkpositive.org/
Jeffrey M. Sturm BS, MA, MBA
Research Acceleration Committee Member
Clinical Trials Committee Member
Board Member ALK Positive, Inc. www.alkpositive.org
Advisory Board Member, UofMichigan ALK NSCLC Research Initiative
10-year ALK Positive NSCLC Survivor
