INNV-29. Clinical and imaging response to ivosidenib for progressive isocitrate dehydrogenase-1 (IDH-1) mutated clival chordoma

BACKGROUND Chordoma is a rare but aggressive malignant tumor that occurs in the skull base and spine. Currently, there are no FDA approved drug therapies to treat chordoma. Tissue molecular profile testing may help illuminate potential targeted therapies. CASE: We present the case of a 72-year-old female with recurrent clival chordoma whose tissue next-generation sequencing (NGS) revealed an IDH-1 mutation. The patient had radiographic progressive chordoma with no further surgical options. She also had worsening clinical symptoms including chronic head pressure, left ear pain, drooling, diplopia, and right arm numbness. She started ivosidenib 500 mg daily. RESULTS MRI prior to initiating therapy showed a large multi-lobular mass centered within the left clivus with extension into the left nasopharynx and left prepontine cistern. Her repeat MRI after nine months of therapy with ivosidenib 500 mg daily showed an approximately 10% reduction in size of the mass. The patient also had improvement in quality of life, with resolution of chronic headaches, stabilization of her visual field deficit, and resolution of right arm numbness. She did not experience any persistent side effects from ivosidenib and routine laboratory results remained within treatment parameters. CONCLUSION This case demonstrates the safety and tolerability of ivosidenib in the treatment of IDH-1 mutated clival chordoma. While the patient has not yet had an objective response based on RECIST criteria with nine months of ivosidenib treatment, her imaging clearly shows shrinkage of the tumor. The patient also had improvement in her quality of life with ivosidenib and has not had worsening neurological symptoms. Her case highlights the utility of NGS for chordoma in identifying potentially repurposed targeted therapies.