Background: Building on our preclinical data, we proposed that combination of low dose TMZ and PCB may overcome TMZ chemoresistance in MGMT unmethylated GBM. We proposed adding Cilengitide, a selective αvβ3 and αvβ5 integrin inhibitor, to PCB, TMZ and RT. Methods: Newly diagnosed GBM pts with unmethylated MGMT received cilengitide 2000 mg twice weekly over 18 months. On week 2 of cilengitide, RT (60 Gy, 2 Gy per fraction) was started for 6 weeks with daily TMZ (60 mg/m2) and PCB (50 mg if BSA < 1.7; 100 mg if BSA ≥ 1.7) followed by 6 cycles of adjuvant TMZ (50mg/m2 in first cycle, 60 mg/m2in subsequent cycles) and PCB (50 mg if BSA < 1.7; 100 mg if BSA ≥ 1.7) given D1 to 20 every 28 days. The primary endpoint was 12m Overall Survival (12 mOS). The probability of accepting insufficiently active treatment was set to 10% and the probability of rejecting an active treatment was set to 20%. If 16 of 29 pts (55%) or less were alive at one year, the treatment was to be declared inactive. Secondary endpoints include 6-month progression-free survival (6mPFS) and toxicity. Results: MGMT was tested in 60 pts to enrol 29 evaluable GBM pts with unmethylated MGMT status (median age: 55 y, range 24-74 y; 11 women and 18 men). ECOG status was 0, 1 and 2 in 16, 11 and 2 pts, respectively. The last pt was enrolled in June 2013 and at time of submission of this abstract 18 of 29 included pts (62%) were alive, 11 (38%) who have been followed-up for a year or more and 7 (24%) less than a year. Current median OS and PFS are 58 (95% CI 44-72) and 30 (95% CI 20-39) weeks respectively. Grade (G) 3 and 4 toxicities included thromboembolism (1 G 4 and 2 G3), seizures (1 G4 and 2 G3), neutropenia without fever (5 G3) and asymptomatic elevated transaminases (1 G4 and 6 G3). Conclusions: The safety profile of the combination was confirmed. As of Jan 2014, the 12mOS has not yet been reached. Of the 7 pts still alive, 5 will need to survive 12 months or more after enrolment for the primary endpoint of 12 mOS to be met. Updated endpoints, including 12 mOS, will be available and presented at the ASCO annual meeting. Clinical trial information: NCT01124240.