Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today announced that perifosine, its oral AKT inhibitor, combined with temsirolimus ("TEM"), was well tolerated in an investigator driven Phase 1 clinical trial in recurrent or progressive malignant glioma ("MG"). Data were presented over the weekend by Thomas J. Kaley, MD, Director, Neuro-Oncology Fellowship Program at Memorial Sloan-Kettering Cancer Center, during a poster session at the Society of Neuro-Oncology annual meeting in Washington D.C.
The trial involved 32 patients with recurrent or progressive (glioblastoma (16), anaplastic astrocytoma (7), anaplastic oligodendroglioma (7), and transformed low-grade gliomas (2)), with median Karnofsky Performance Status ("KPS") 80 (range, 60-100). Twenty-one patients were refractory to bevacizumab or other anti-VEGF/VEGFR therapy. The dose of TEM was escalated in each cohort using standard 3 + 3 design from 15 mg to 170 mg administered once weekly. The dose of perifosine was a 600 mg loading dose on day 1, followed by a 100 mg nightly dose, for dose level 1 through dose level 6. At dose level 7, the loading dose was increased to 900 mg, followed by a 100 mg nightly dose.
The trial is currently accruing to dose level 5 (115 mg) after 2 dose-limiting toxicities ("DLT") in the dose level 7 (170 mg) and dose level 6 (170 mg) expansion cohorts. Maximum tolerated dose ("MTD") was not defined. Thirty-one patients were evaluable for toxicity. There were 5 DLTs: thrombocytopenia (3), intra-cerebral hemorrhage (1), and lung infection (1). Only one grade 4 toxicity (thrombocytopenia) was reported. Most frequent grade 3 non dose-limiting hematologic toxicities were lymphopenia (7), hyperglycemia (4), lung infection (4), and hypophosphatemia (3). Notable grade 2 toxicities were hypophosphatemia (14), hypocholesterolemia (13), and hypertriglyceridemia (11).
Preliminary survival results demonstrated that median overall survival was 7.4 months. There were 27 radiographic responses: complete response (0), partial response (2), stable disease (13) and progressive disease (12).
Combination therapy with TEM ≥ 115 mg weekly and perifosine 100 mg daily (following 600 mg load) was well tolerated in heavily pre-treated adults with recurrent MGs. Accrual ongoing at dose level 5 and MTD has not yet been defined.
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