UCSF

Abstract

BACKGROUND

GBM patients who progress on BEV, an approved angiogenesis inhibitor for recurrent GBM, have a dismal outcome with a median survival of < 6 months. DUR is a human IgG1 monoclonal Ab against PD-L1.

METHODS

This ongoing Phase 2 open-label study (NCT02336165) evaluates safety and efficacy of DUR (10 mg/kg every 2 weeks [Q2W]) in 5 GBM cohorts. Results are presented for Cohort C (DUR + continuing BEV 10 mg/kg Q2W in BEV-refractory recurrent GBM). The primary efficacy endpoint for Cohort C is overall survival at 6 months (OS-6), based on modified RANO criteria by investigator assessment; secondary endpoints include safety/tolerability and progression-free survival (PFS). The Intent-to-treat population includes patients receiving any dose of DUR and having at least baseline and 1 post-baseline tumor assessment.

RESULTS

First patient treated: 24 Mar 2015; data cutoff: 15 Mar 2017. Cohort C completed enrollment of 22 patients (male: 63.6%; mean age: 54.8 [37–77] years; baseline ECOG PS0: 27.3%, PS1: 68.2%; baseline measurable lesions: 81.8%). Treatment-emergent adverse events (TEAEs) occurred in 19 (86.4%) patients and most commonly included neurologic events associated with GBM. Treatment-related AEs (TRAEs) occurred in 10 (45.5%) patients, and incidences by maximum CTCAE grade (Gr) were Gr1: 5 (22.7%); Gr2: 4 (18.2%); Gr3: 1 (4.5%; fatigue); and Gr4/5: 0 patients. Most common TRAEs (≥2 [9.1%] patients) were fatigue, increased ALT, constipation, and headache. All patients (n=22) were evaluable for efficacy: OS range, 0.9 - 51.6 weeks; 8 patients (36%) had OS ≥ 22 weeks; PFS range, 0.9 -24.4 weeks; 11 patients (50%) had PFS ≥ 8 weeks; 3 patients were still alive at cutoff date; OS-6 to follow.

CONCLUSIONS

DUR + continuing BEV therapy appears to be well tolerated and shows preliminary activity in BEV-refractory recurrent GBM. Further studies are warranted.