Gilteritinib for the Treatment of ALK positive non-small cell lung cancer (NSCLC

Phase 1 Clinical Trial NCT06225427 by The University of Michigan Rogel Cancer Center and Astellas Pharma Inc.

Gilteritinib for the Treatment of ALK positive non-small cell lung cancer (NSCLC)

https://www.clinicaltrials.gov/study/NCT06225427

Principal Investigator: Dr. Angel Qin qina@med.umich.edu

This trial is for patients with Stage 4 ALK positive NSCLC that have progressed on an earlier generation ALK TKI AND lorlatinib, and on any number of other standard-of-care or trial treatments. The trial drug is gilteritinib (aka Xospata), which was approved by the FDA in 2018 for a type of leukemia, but has been shown to have activity against ALK NSCLC in patient-derived models (mice with transplanted human cancer). Gilteritinib is in effect a pan-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. Patients diagnosed with Alk positive adeno, squamous, or adenosquamous NSCLC are eligible. Estimated enrollment is thirty patients. Applicants must be at least 18 years of age.

This phase I trial will study the safety, side effects, and best dose of gilteritinib in treating patients with stage IV ALK NSCLC. Although already approved for a type of leukemia, a blood and bone marrow disease, ALK positive NSCLC produces solid tumors, and the safety and best dose may be different than for leukemia. Thus the need for a phase I 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). Based on side effects and tolerability, the dose will either remain at 120mg or be decreased. One of the other key objectives is to evaluate the response to gilteritinib based on MRI and CT imaging. Clinical Intracranial response and disease control will be assessed. Patient’s circulating tumor cells (CTCs) will also be studied.

A new pre-treatment biopsy, if one has not been obtained, is HIGHLY encouraged but not required for enrollment, as tissue can also be submitted to the Judith Tam ALK Lung Cancer Research Initiative (JTARI) for testing against a panel of ALK NSCLC drugs and chemotherapy agents to determine other potential options for the patient. Archival tissue, if available and accessible, is acceptable. Patients with brain metastasis are allowed, but must have been treated prior to the trial.

The location for the Phase I trial is the Rogel Cancer Center on the University of Michigan campus in Ann Arbor, Michigan. Dr. Angel Qin, co-lead of the Judith Tam Initiative (JTARI), is the Principal Investigator, and primary contact (see above). Patients must be able to travel to UMichigan, and for the first of the 21-day cycles participants will come into the clinic once a week. For all subsequent cycles, participants will come in once every cycle (every 21 days). A required washout period from prior drug treatments is at least seven days. Baseline scans may be done locally; however, all subsequent blood draws and scans must be done at UM. Certain procedures may need to be covered by the patient’s insurance, so it is recommended that interested applicants check that the Regents of the University of Michigan is in-network, and or that their insurance has out-of-network benefits.

The University of Michigan Judith Tam ALK Lung Cancer Research Initiative is made possible by a $7.6M gift from the Judith and Richard Tam Foundation. The gift is intended to accelerate progress in discoveries related to the pathogenesis, progression, treatment, and prevention of ALK driven lung cancers. The overarching purpose is to foster rapid adoption of key discoveries that directly enhance the quality and length of patients’ lives. UMichigan has assembled a team of clinical and scientific experts in cancer metastasis, thoracic oncology, thoracic surgery, genetics, molecular pharmacology, cell biology, pathology, organoid development, data science, biomedical engineering, and other specialties. Since its inception in late 2021 the UMichigan ALK Initiative team has made extraordinary progress in achieving its objectives; assembling a talented staff, establishing strong platforms, developing a solid strategic plan, and advancing the science beyond previous limits. https://www.rogelcancercenter.org/judith-tam-alk-lung-cancer-research-initiative

Astellas Pharma is a multinational pharmaceutical company with headquarters in Tokyo, Japan, and subsidiaries worldwide, including Astellas Pharma US in Northbrook, Illinois. This 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, UMichigan, and ALK Positive, leading to the trial’s approval by all parties and opening for recruitment in April 2024. This trial is supported by a grant approved by the ALK Positive, Inc. Grant Review Committee, and funding is provided by the patients that participate in the ALK Positive support group on Facebook, and the much larger community of ALK patients and caregivers worldwide. 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/

Author: Jeffrey M. Sturm BS, MA, MBA

ALK Positive, Inc.

Clinical Trials Committee

Advisory Board, UofMichigan ALK Lung Cancer Research Initiative

Nine Year ALK Positive NSCLC Survivor