Corvus Starts Phase 2 Trial of Soquelitinib for ALPS Patients

Corvus Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company, has announced the initiation of a Phase 2 clinical trial by the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health (NIH), to evaluate soquelitinib for treating autoimmune lymphoproliferative syndrome (ALPS). This rare genetic disorder is characterized by immune system dysregulation, primarily affecting T cells. The trial is led by Dr. V. Koneti Rao, a Senior Research Physician at the NIH Clinical Center, known for his previous work on soquelitinib's potential for ALPS patients. Additional trial sites include the Children’s Hospital of Philadelphia and the Texas Children’s Cancer and Hematology Center.

ALPS often emerges in early childhood and most commonly results from a mutation in the Fas gene. This gene mutation leads to a deficiency in the Fas protein, which is crucial for apoptosis, the process of programmed cell death. Without proper functioning of this protein, T cells accumulate excessively, disrupting normal immune function and causing serious symptoms such as autoimmune diseases and increased risk of lymphoma. Patients with ALPS typically experience symptoms like cytopenias (low blood cell counts), lymphadenopathy (enlarged lymph nodes), and splenomegaly (enlarged spleen), with treatments traditionally focusing on symptom management rather than cure.

The Phase 2 trial aims to enroll up to 30 patients aged 16 and above, confirmed to have ALPS-FAS through genetic testing. Participants will be divided into two dosing groups to receive either 200 mg or 400 mg of soquelitinib twice daily for up to 360 days. The primary goal is to assess the drug's effectiveness by measuring reductions in spleen and lymph node sizes using CT or PET/CT scans. Improvements in blood cell counts, which are crucial for alleviating symptoms like anemia and thrombocytopenia, will also be monitored. Secondary objectives include evaluating the safety and tolerability of the drug.

Soquelitinib is designed to inhibit the interleukin-2-inducible T-cell kinase (ITK), an enzyme key to T cell and natural killer cell functions. This investigational drug has shown promise in preclinical models by affecting T cell differentiation, promoting the generation of Th1 helper cells while inhibiting Th2 and Th17 cells, which are associated with autoimmune and allergic conditions. The mechanism by which soquelitinib operates may offer therapeutic advantages for a range of conditions, including cancers and immune disorders.

Corvus Pharmaceuticals is also exploring soquelitinib in other clinical trials, including a registrational Phase 3 trial for peripheral T cell lymphoma (PTCL) and a Phase 1 trial for atopic dermatitis. The company plans to further investigate its potential in solid tumors starting in the second quarter of 2025. The exploration of ITK inhibition by Corvus represents a novel approach in immunotherapy, aiming to restore immune balance and improve outcomes in both cancer and autoimmune diseases.

This new Phase 2 trial for ALPS underscores the potential for soquelitinib to address the challenging symptoms associated with T cell dysregulation. By targeting the underlying genetic and molecular components of the disease, Corvus and its partners at NIH/NIAID aim to provide a more effective treatment strategy for this debilitating condition that currently lacks adequate therapeutic options. The collaboration highlights the ongoing efforts to advance targeted therapies that offer hope for improving the quality of life for patients living with rare genetic diseases like ALPS.