Phase Ib/II Study of Buparlisib Plus Carboplatin or Lomustine in Patients With Recurrent Glioblastoma Multiforme

Inclusion Criteria:

- Patient is an adult ≥ 18 years old at the time of informed consent.

- Patient has histologically confirmed diagnosis of GBM with documented recurrence after
first line treatment including radiotherapy and TMZ (SoC), not suitable for curative
surgery or re-irradiation.

- Patient has at least one measurable and/or non-measurable lesion as per RANO criteria

- Patient has recovered (to Grade ≤1) from all clinically significant toxicities related
to prior antineoplastic therapies.

- Patient has Karnofsky performance status (KPS) ≥70%.

- Patient has adequate organ and bone marrow functions:

- Absolute Neutrophils Count (ANC) ≥ 1.5 x 109/L

- Platelets ≥ 100 x 109/L (in case of transfusion stable for ≥14 days prior to
treatment start)

- Hemoglobin ≥ 9.0 g/dL (in case of transfusion stable for ≥14 days prior to
treatment start)

- INR ≤ 1,5

- Serum Creatinine ≤ 1.5 x ULN, or Creatinine Clearance > 45mL/min

- Potassium and calcium (corrected for albumin), sodium and magnesium within
institutional normal limits

- Serum Bilirubin ≤ ULN, AST and ALT ≤ ULN

- HbA1c ≤ 8%

- Fasting plasma glucose (FPG) ≤ 120 mg/dL or ≤ 6.7 mmol/L

- Patient has tumor tissues available (archival or fresh).

Exclusion Criteria:

- Patient has received previous treatment with PI3K inhibitors, lomustine or
carboplatin.

- Patient has received previous antineoplastic treatment for recurrent GBM (e.g. VEGF
inhibitors, cytotoxic agents).

- Patient has received more than one line of cytotoxic chemotherapy

- Patient has concurrent use of anti-neoplastic agents including investigational therapy

- Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight
heparin (LMWH), or fondaparinux is allowed.

- Patient is currently receiving treatment with drugs known to be moderate or strong
inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong
inducers for at least one week and must have discontinued strong inhibitors before the
treatment is initiated. Switching to a different medication prior to randomization is
allowed.

- Patient is currently receiving an enzyme-inducing anti-epileptic drug (EIAED). The
patient must have discontinued EIAED therapy for at least two weeks prior to starting
study drug.

Other protocol-defined Inclusion/exclusion criteria may apply.