CTNI-25. CASE STUDY OF AN EXCEPTIONAL RESPONDER: ENZASTAURIN LONG TERM EFFICACY IN A PATIENT WITH PRIMARY AND RECURRENT GLIOBLASTOMA MULTIFORME (GBM)

Enzastaurin (ENZA, DB102) is an oral serine/threonine kinase inhibitor targeting the protein kinase C (PKC) and phosphoinositide 3-kinase (PI3K)/AKT pathways to inhibit tumor cell proliferation, induce tumor cell apoptosis, and suppress tumor-induced angiogenesis. We report the long-term clinical response of a GBM patient treated with ENZA who has survived for 15 years from initial diagnosis, despite tumor recurrence 5 years ago. In 2006, the 44-year-old man was diagnosed with GBM and underwent surgical resection of the tumor. He subsequently enrolled in a Phase I/II trial evaluating ENZA in newly diagnosed GBM and gliosarcoma (NCT00402116), in September 2006. He was treated with radiation and concurrent temozolomide (TMZ) + ENZA, followed by adjuvant TMZ + ENZA, which he tolerated well. He stopped treatment electively in November 2010, after 51 adjuvant cycles, in the setting of stable imaging without evidence of tumor activity. The patient did well until January 2016, when a serial MRI scan showed tumor progression; he underwent a second surgical resection (pathology: recurrent GBM, IDH1 R132H neg, ATRX retained, EGFR amplified, MGMT methylated) followed by re-irradiation with concurrent TMZ. Given the patient’s prior prolonged disease control, he started a compassionate treatment of ENZA in combination with adjuvant TMZ in April 2016. TMZ was stopped in June 2018 after 28 cycles; he continues single agent ENZA to date, with no evidence of tumor progression as of May 2021. Consistent with DGM1 (Denovo Genomic Marker 1) being an ENZA efficacy predicting biomarker, the patient is DGM1 positive. This case provides clinical evidence that the addition of ENZA to standard of care may provide substantial long-term benefit in DGM1 positive patients with GBM. A Phase 3 study of ENZA in DGM1 positive newly diagnosed GBM patients is currently ongoing (ENGAGE study, NCT03776071).