Background: BKM120 is an oral pan-class I PI3 kinase (PI3K) inhibitor, with demonstrated CNS penetration. Enhanced PI3K signaling is common in GBM (56-75% of cases), and is associated with poor survival (Chakravarti et al, 2004). This phase I study was designed to determine the maximum tolerated dose (MTD) of BKM120 in combination with a standard dose of bevacizumab as treatment for patients with relapsed/refractory GBM or other refractory solid tumors. Methods: Patients with relapsed/refractory GBM or other refractory solid tumors for which bevacizumab was an appropriate therapy received BKM120 with bevacizumab in a standard 3+3 dose escalation design. Bevacizumab 10 mg/kg IV was administered days 1 and 15 of 28-day cycles, with escalating doses of BKM 120 self-administered daily. Patients were evaluated for response after 8 weeks; treatment continued until disease progression or unacceptable toxicity. Results: Twelve patients were treated at 2 BKM120 dose levels, DL 1 = 60 mg/day and DL 2 = 80 mg/day. DL 1 (n = 6) tumor types included: 2 GBM, 2 colorectal and 2 NSCLC with treated brain metastases. Dose-limiting toxicity (DLT) of G4 delirium was observed in 1 GBM patient. Three additional patients were enrolled, and no further DLTs occurred. DL 2 (n = 6) tumor types included: 3 GBM and 3 colorectal. DLTs were observed in 2 of 6 patients: 1 colorectal (G3 rash, G3 stomatitis, G3 dehydration, and G2 worsening vomiting), and 1 GBM (G3 ataxia and G3 mental status changes). 6 patients had CNS symptoms possibly related to treatment, including mood alteration (3 GBM and 1 colorectal), delirium, hallucinations, and mental status change (1 GBM patient each). Common treatment-related toxicities (all grades) included: dyspepsia (42%), nausea (33%), ALT elevation (25%), dehydration (25%), proteinuria (25%), rash (25%), and thrombocytopenia (25%). No objective responses were documented; however, 1 colorectal patient remains on treatment with stable disease for 8 months. Conclusions: The addition of BKM120 to standard dose bevacizumab was tolerated at a dose of 60 mg/day. A phase II study with this combination is currently underway in patients with relapsed/refractory GBM. Clinical trial information: NCT01349660.