This is a first-in-man, phase I/II clinical research study with BEZ235, an inhibitor of phosphatidylinositol 3'-kinase (PI3K). The study consists of a Phase I dose escalation part followed by a safety expansion part and a Phase II expansion part:

Phase I dose escalation part (advanced solid tumors):

Patients receive oral BEZ235 once daily on days 1-28 of the first course. Courses will repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of at least 3 patients receive escalating doses of BEZ235 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose expected to produce during the first course of treatment dose-limiting toxicity in 33% of patients.

Once the MTD has been defined, the safety expansion and efficacy expansion parts of the trial will be opened for enrollment.

Phase I safety expansion part (advanced solid tumors):

Patients will be treated with BEZ235, given at the MTD, once daily. Treatment of patients will continue until disease progression or occurrence of unacceptable side effects.

Phase II expansion part (advanced breast cancer):

Patients will be treated with BEZ235, given at the MTD, once daily. Treatment of patients will continue until disease progression or occurrence of unacceptable side effects.

An effort will be made to enrich the trial population with Cowden Syndrome patients with advanced solid malignancies.

• Solid Tumors
• Breast Cancer

• Experimental: Dose Escalation
• Experimental: MTD Expansion

Inclusion Criteria:

[Single agent dose escalation arm]: Patients with histologically-confirmed, advanced unresectable solid tumors including CS patients who have progressed on (or not been able to tolerate) standard therapy within three months before screening visit or for whom no standard anticancer therapy exists.

[Combination Dose Escalation arm]: Female patients with histologically confirmed, metastatic HER2+ Breast Cancer, after failure of trastuzumab treatment. Eligible patients will have to have tumors carrying molecular alterations of PIK3CA and/or PTEN.

[Single agent safety expansion arm]: Patients with histologically-confirmed, advanced unresectable solid tumors including CS patients who have progressed on (or not been able to tolerate) standard therapy within three months before screening visit or for whom no standard anticancer therapy exists. Patients will be pre-screened for molecular alterations affecting PIK3CA and/or PTEN. Patients with NSCLC will be pre-screened for EGFR mutation.

Age ≥ 18

Exclusion Criteria:

-Patients who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.

Prior treatment with a PI3K inhibitor-Acute or chronic liver disease or renal disease Acute or chronic pancreatitis Patients with any peripheral neuropathy ≥ CTCAE grade 2 Patients with unresolved diarrhea ≥ CTCAE grade 2

Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:

• Impaired cardiac function or clinically significant cardiac diseases
• Patients with diabetes mellitus requiring insulin treatment, history of gestational diabetes mellitus
• Patients with known coagulopathies (as per amendment 4)
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol Patients with a history of photosensitivity reactions to other drugs

Any of the following ophthalmological findings:

• Progressive eye disease that could lead to severe loss of visual acuity or visual field loss during the study period
• Inability to perform the ophthalmic procedures required in this protocol

Other protocol-defined inclusion/exclusion criteria may apply