The purpose of this study is to learn whether the study drugs avutometinib and defactinib can help stop or shrink malignant peripheral nerve sheath tumors (MPNST) that have returned or cannot be removed with surgery.
Age > 12 years old with a body surface area (BSA) of at least 1.5 mm2
DIAGNOSIS: Participants with relapsed, refractory, unresectable or metastatic histologically confirmed NF1 associated or sporadic MPNST.
Participants must have available archival tissue. Tissue blocks strongly preferred. Exceptions may be made following discussion with study team if tissue has been exhausted.
MEASURABLE DISEASE: Participants must have measurable disease by RECIST v1.1.
Current warfarin use. If a participant is currently being treated for a pulmonary embolism with warfarin, they may be eligible if they are able to be converted to a Direct Oral Anticoagulant (DOAC) or low molecular weight heparin.
History of another active malignancy. Prior malignancy, that has been curatively treated or malignancies with very low potential for recurrence or progression may be included.
Major surgery within 4 weeks (excluding placement of vascular access, or core needle biopsy), minor surgery within 2 weeks.
Exposure to medications (with or without prescription), supplements, herbal remedies, or foods with potential for drug-drug interactions with avutometinib and/or defactinib within 5 half-lives (if known), or 14 days prior to the first dose of study intervention, whichever is longer.
Girish Dhall, MD
Lead sponsor
University of Alabama at Birmingham
Sponsor institution
United States Department of Defense
Collaborator
Children's Hospital of Philadelphia
Collaborator
Washington University School of Medicine
Collaborator