Vanderbilt-Ingram Cancer Center

Patients are being asked to take part in a research study. This is because they have advanced cancer that has not responded to standard therapy, or has recurred or progressed after standard therapy, or for which there is no standard therapy available. One of the study drugs being used in this clinical trial is a monoclonal antibody (Mab) called SAR256212. A Mab is a type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. SAR256212 is a human Mab that binds to a protein called Erb3. This protein affects the growth of tumor cells. The other study drug is SAR245408. This drug binds to and inhibits the activity of certain proteins in the body known as phosphatidylinositol 3-kinases (PI3Ks). These proteins affect the growth of some tumor cells. Both these drugs are investigational products. This means they are not approved by the US Food and Drug Administration (FDA) or in any country outside of the United States. The main purpose of this study is to determine the maximum tolerated dose of SAR256212 and SAR245408 used together in patients with solid tumor cancers. The study will also want to learn: -The safety profile of SAR245408 in combination with SAR256212 -The overall response rate and change in tumor size - The levels of the 2 drugs in the blood This study is being conducted at 3 to 4 clinical sites in the US. About 56 patients will take part in the study. About 18 to 25 patients will take part at Vanderbilt. The total time that patients will take part in the study will be 6 to 12 months.

Criteria
 Inclusion criteria:

 • Metastatic or locally advanced nonhematological cancer, for which no alternative therapy is available

 • Written informed consent

 • For dose expansion only:

 • Patient's tumor harbors activating mutations in phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA)

 • Tissue from archived sample

 • Measurable and evaluable disease

 Exclusion criteria:

 • Patient less than 18 years old

 • ECOG (Eastern Cooperative Oncology Group) performance status >2

 • Any serious active disease or comorbid condition, which, in the opinion of the Investigator, could interfere with the safety of the patient or the ability of the patient to comply with the study, or with the interpretation of the results

 • Poor bone marrow reserve as defined by absolute neutrophils count <1.5 x 109/L or platelets <100 x 109/L

 • Poor organ function as defined by 1 of the following:

 • Total bilirubin >1.5 x ULN (upper limit of normal)

 • AST (aspartate aminotransferase) and/or ALT (alanine aminotransferase) >2.5 x ULN

 • Serum creatinine >1.5 x ULN and/or creatinine clearance <60 mL/min

 • PT/ (INR) (prothrombin time) (International Normalized Ratio) and/or partial thromboplastin time (PTT) test results ≥1.3 ULN

 • Pregnant or breast-feeding women

 • No use of effective birth control methods, when applicable

 • No resolution of all specific toxicities (excluding alopecia) related to any prior anticancer therapy to Grade ≤1 according to the NCI common terminology criteria for adverse events (CTCAE) v.4.0

 • Any of the following within 6 months prior to enrollment: myocardial infarction, severe/unstable angina, or coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant cardiac arrhythmias (Grade 3/4)

 • Baseline corrected QT interval (QTc) >460 ms.

 • NYHA Class III (New York Heart Association) or IV congestive heart failure or LVEF (left ventricular ejection fraction) < the lower limit of normal (LLN) for institution

 • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including cytomegalovirus, Epstein-Barr virus, toxoplasmosis, and hepatitis B and C, positive for the human immunodeficiency virus (HIV), hypertension, or uncontrolled diabetes.

 • Previous treatment with a selective PI3K inhibitor (phosphoinositide-3-kinase, catalytic, alpha polypeptide), mTOR (mechanistic target of rapamycin) inhibitor, or AKT inhibitor (v-akt murine thymoma viral oncogene homolog 1)

 • Known hypersensitivity to the investigational medicinal product(s) or to its excipients, or patient who has had hypersensitivity reactions to fully human monoclonal antibodies

 • Cytotoxic chemotherapy (including investigational cytotoxic agents) or biologic agents (antibodies, immune modulators, cytokines) within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks, before the first dose of study treatment

 • Prior radiation therapy within 2 weeks before the first dose of study treatment

 • Prior major surgery from which the patient has not recovered or stabilized

 • Any other investigational therapy within 4 weeks prior to the first dose of study treatment

 • Brain tumor or brain metastasis are considered eligible if the patient has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for 2 or more weeks

 • Ongoing anticoagulation with therapeutic doses of warfarin (low-dose warfarin ≤1 mg/day is permitted).

 • HBA1C (hemoglobin A1c) >7 or any patient requiring medication for glycemic control

 The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.