ATIM-21. UPDATED RESULTS OF A PHASE I TRIAL OF ANTI-LAG-3 OR ANTI-CD137 ALONE AND IN COMBINATION WITH ANTI-PD-1 IN PATIENTS WITH RECURRENT GBM

Abstract

BACKGROUND: Given the success of immunotherapy in other solid tumors, immunotherapy is being actively investigated in GBM. Preclinical data with the checkpoint molecules anti-Lag-3 and anti-CD137 have effectively induced an anti-tumor immune response with resultant improved survival when combined with anti-PD-1. METHODS: The Adult Brain Tumor Consortium (ABTC) 1501 trial is a phase I, open label, multicenter, multiarm dose-finding/safety study of anti-LAG-3 (BMS-986016) or anti-CD137 (BMS-663513) alone and in combination with anti-PD-1 in patients at first recurrence of GBM. The primary objective is to define MTD for the mono and combinational treatment. The major secondary objective is to explore for a signal in efficacy. The key inclusion criteria are adults, first recurrence of GBM following RT+TMZ, TLC≥1000/ul, KPS≥ 60%, stable corticosteroid regimen, measurable disease, and written informed consent. Sequential allocation is used for the treatment assignment at starting dose of 80mg for anti-LAG-3 and 8mg for anti-CD137. Anti-PD-1will be given at a flat dose of 240 mg in the combination treatment arms. The 3 + 3 design is used for the dose finding with a target DLT rate ≤ 33%. RESULTS: 7 patients have been enrolled in the initial single dose arms with an average age at 60 and KPS at 80%. Three patients were treated with anti-LAG-3 at 80 mg and 4 patients were on 8mg anti-CD137. One patient had a grade 2 headache attributed to anti-CD137. There were a grade 2 fatigue and a grade 3 leukocytosis attributed to anti-LAG-3. No DLT was observed. CONCLUSIONS: The trial is ongoing. The first dose of both anti-LAG-3 and anti-CD137 were well tolerated. The single agent arms and a combination arm with anti-PD-1 are open for accrual.