Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients

Study Description: This is a multisite open-label phase 2a study to evaluate the safety, tolerability, and preliminary efficacy of the interleukin (IL)-2 inducible T-cell kinase (ITK) inhibitor soquelitinib for treating ALPS-FAS. This study will be conducted in two stages. In the first stage, following a background drug washout of up to 90 days, 8 participants will receive 200 mg of soquelitinib twice daily for up to 360 days, with approximately monthly study visits (in person or remote). A safety and futility interim analysis will be conducted after all 8 participants have had a computed tomography (CT) or positron emission tomography (PET)/CT scan at day 90 and have completed at least 80% of their study drug regimen. If at least one participant has a positive response to the study drug and there are no safety concerns among the 8 participants, then the study will proceed to stage 2, in which 6 new participants will be enrolled and, following a background drug washout of up to 90 days, receive the same dosage as stage 1 (200 mg twice daily for 360 days). Individual participation concludes at the end of the 360-day regimen. Participants may re-enroll once in the study. They will repeat the whole study schedule except for the screening visit, but they will have a study drug washout period of up to 90 days with monthly visits during that time. Upon reaching pre-specified criteria, they will begin a second 360-day regimen of soquelitinib at 200 mg twice daily. The primary endpoints will be assessed after all 6 participants of stage 2 have had a CT or PET/CT scan at day 90 and have completed at least 80% of their study drug regimen. The trial will automatically be determined a failure if safety concerns or lack of positive response prevent progression to stage 2. Primary Objectives: To determine the efficacy of soquelitinib in reducing spleen volume or target lymph node volume in people with ALPS-FAS. Secondary Objective: 1. To determine the efficacy of soquelitinib in improvement of lymphoproliferation and autoimmune disease, including cytopenias, in people with ALPS-FAS. 2. To determine the safety and tolerability of soquelitinib in people with ALPS-FAS. Primary Endpoints: Reduction of spleen volume or target lymph node volume by 25% from baseline to day 90, assessed by CT or PET/CT scan. Secondary Endpoints: 1. Shrinkage in spleen volume from baseline to day 90. 2. Shrinkage in target lymph node volume from baseline to day 90. 3. Reduction of cytopenias by one severity level from baseline to day 90. 4. Reduction in prednisone dosage. 5. Grade 3 or 4 systemic infections within 360 days (first or second regimen). 6. Clinically significant worsening of viral, mycobacterial, or fungal infection requiring new treatment or change of treatment by day 360 (first or second regimen). 7. Any drug-related grade 3 or 4 adverse event (AE) that triggers a pause.